On October 1, 2019 LineaRx, Inc., the majority-owned subsidiary of Applied DNA Sciences, Inc. (NASDAQ: APDN) focused on next-generation biotherapeutics, reported that its invasive Circulating Tumor Cells (iCTCs) platform demonstrated superior correlation over Prostate Specific Antigen (PSA) in an ongoing Phase II trial in recurrent prostate cancer (Press release, Applied DNA Sciences, OCT 1, 2019, View Source [SID1234539966]). Most notably, the concentration of rare iCTCs identified per milliliter of whole blood correlated more directly with disease status than did the levels of PSA. These iCTCs were captured and identified utilizing LineaRx’s technology platform recently acquired from Vitatex Inc.

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LineaRx’s collaborator Tyme Technologies, Inc. (NASDAQ: TYME), reported yesterday results of this recently completed Phase II trial using SM-88 to treat recurrent prostate cancer at the Congress of the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper), one of the preeminent meetings for highlighting new cancer therapies and diagnostics. The study updated the safety and antitumor effects of SM-88 in men with non-castrate non-metastatic prostate cancer. Antitumor effects were assessed by post-therapy changes in PSA and the number of iCTCs. Results showed that patients treated with this oral non-hormonal therapy maintained metastases-free survival without testosterone deprivation or typical hormonal therapy side effects.

Dr. Wen-Tien Chen, Principal Investigator of CTC Programs at LineaRx stated: "This use of iCTC quantification for providing earlier and more accurate identification of prostate cancer shows the importance of running trials using the iCTC functional capture and identification system from LineaRx. Published studies have shown that the concentration of iCTCs in blood correlates with disease status across other hard tumors, including metastatic sarcoma, pancreatic, ovarian, breast, lung and colorectal cancers. We believe our proprietary platform can help diagnose these difficult cancers earlier and with superior predictive capability."

The current reported SM-88 Phase II study examines iCTCs in prostate cancer for what we believe is the first time in a clinical trial. While PSA has historically been the recognized biomarker for prostate cancer, many studies over the last 20 years have shown it is an inadequate biomarker, since it may become elevated in patients with no apparent disease, or less serious pathology than cancer. Intensive efforts have been directed towards alternative prostate cancer biomarkers, particularly those that can predict disease aggressiveness and help to drive better treatment decisions. However, biomarker research has centered on disease diagnostics, rather than prognosis and prediction, which could work toward disease prevention—an important focus moving forward.

The authors concluded: "Reductions in iCTC number may be a more informative indicator of benefit than changes in PSA." Dr. Chen added, "New prostate cancer biomarkers should be targeted to addressing unmet clinical needs in prostate cancer management, including indicators for disease with low PSA values (<10ng/mL), prognostic markers to distinguish indolent from aggressive disease, and biomarkers for metastatic cancer."

LineaRx’s iCTC technology is unique in that it isolates iCTCs on a functional basis (the invasion of a model tissue for the extracellular matrix, or the tissue between cells in an organ) and allows the cells to be cultured for deeper genomic analysis. iCTCs are a model for metastasis, since the tumor cells have left the primary tumor and entered the circulation. The LineaRx platform may serve as a standalone device or as a front-end to increase the sensitivity of approved diagnostics.

"iCTCs have the potential for metastasis, and may be very useful in the diagnosis of cancer, even before tumors may be imaged," said Dr. James Hayward, CEO of LineaRx. "The present study is exciting because we believe it shows that iCTCs may be used to accurately follow therapy success in this very prevalent cancer while also providing new tools for cell and gene therapy design and production."

On October 1, 2019 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported that new data on IPH5401 and monalizumab were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress in Barcelona, Spain (Press release, Innate Pharma, OCT 1, 2019, View Source [SID1234539965]).

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Poster presentations highlighted:

Preliminary results of STELLAR-001, a Phase I dose-escalation study of IPH5401, an anti-C5aR antibody, in combination with durvalumab in advanced solid tumors;
One-year survival data of the first expansion cohort of the Phase II trial evaluating monalizumab in combination with cetuximab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN)

"We are pleased with the continued progress of monalizumab and IPH5401. We believe that by targeting C5a receptors, IPH5401 is a potentially first-in-class therapeutic antibody for cancer treatment. The preliminary clinical data set from the STELLAR-001 dose-escalation trial prompted us to start and broaden the expansion cohorts in three different settings where anti-PD-(L)1 have shown no or limited activity," said Pierre Dodion, Chief Medical Officer of Innate Pharma. "In addition, the survival data set for the combination of monalizumab and cetuximab in head and neck cancer support further development in IO-pretreated and IO-naïve patients, populations with high unmet medical need."

Key Highlights from IPH5401’s STELLAR-001 Study
In the STELLAR-001 dose-escalation study, 14 patients were included across four doses. Six patients had NSCLC, five had HCC, two had urothelial carcinoma (UCC), and one had renal cell carcinoma (RCC).

The combination of IPH5401 and durvalumab was reported to be well tolerated. No dose limiting toxicity was reported and no dose relationship was observed regarding safety. Pharmacodynamic analyses confirmed full receptor saturation at all dose levels and provided the basis for dose selection for the expansion cohorts.

Twelve patients were evaluated for efficacy. Early activity signals were observed in HCC and NSCLC patients, which included:

One confirmed partial response was reported in a HCC patient with prior progression after nivolumab
One prolonged stable disease (40 weeks) was reported in a NSCLC patient with prior progression after nivolumab

The Company will initiate the planned expansion cohorts in NSCLC patients with secondary resistance to prior IO treatment and in IO-naïve HCC patients to generate additional safety and efficacy data as well as additional translational analyses on tumor biopsies. In addition, based on the data generated in the dose escalation, the Company plans to add an additional cohort testing IPH5401 in combination with durvalumab in IO-pretreated HCC patients, subject to regulatory approval.

Key highlights from the Phase II study of monalizumab in combination with cetuximab in patients with R/M SCCHN, one-year survival data
In a cohort of 40 SCCHN patients previously treated with chemotherapy alone or chemotherapy followed by PD-1/L1 checkpoint inhibitors, the combination of monalizumab and cetuximab demonstrated a manageable safety profile and a response rate of 27.5% (36% and 17% in IO-naïve and IO-pretreated patients, respectively). Responses were observed in platinum-resistant patients and human papillomavirus (HPV) positive and negative patients.

Additional efficacy highlights included:

Median overall survival of 8.5 months with median follow-up time of 17 months;
Trend for improved survival in IO-pretreated patients (14.1 months in IO-pretreated patients and 7.8 months in IO naïve patients); and
12-month overall survival rate of 44% (60% in IO-pretreated and 32% in IO naïve patients)
These data suggest that the combination of monalizumab and cetuximab may provide promising response rates and favorable trends in overall survival. The Company is moving forward with the planned expansion cohorts in IO-pretreated and IO-naïve R/M SCCHN patients.

About IPH5401:
IPH5401 is a potentially first-in-class therapeutic antibody that specifically binds and blocks C5a receptors (C5aR) expressed on subsets of myeloid-derived suppressor cells (MDSC) and neutrophils. Part of the innate immune system, these types of cells promote tumor growth by secreting inflammatory and angiogenic factors, potently suppress anti-tumor T and NK cells and hamper the activities of PD-1 checkpoint inhibitors.

C5a, a factor in the complement cascade, is often overexpressed in tumors, where it attracts and activates MDSCs and neutrophils in the tumor microenvironment. Preliminary evidence suggests high expression of the C5a receptor in both NSCLC and HCC.

About Monalizumab:
Monalizumab is a potentially first-in-class dual checkpoint inhibitor targeting NKG2A receptors expressed on tumor infiltrating cytotoxic CD8+ T cells and NK cells.

NKG2A is an inhibitory checkpoint receptor for HLA-E. By expressing HLA-E, cancer cells can protect themselves from killing by NKG2A+ immune cells. HLA-E is frequently overexpressed in the cancer cells of many solid tumors and hematological malignancies. Hence, monalizumab may re-establish a broad anti-tumor response mediated by NK and T cells. Monalizumab may also enhance the cytotoxic potential of other therapeutic antibodies.

AstraZeneca (LSE/STO/NYSE: AZN) obtained full oncology rights to monalizumab in October 2018 through a co-development and commercialization agreement initiated in 2015. The ongoing clinical development for monalizumab is focused on investigating monalizumab in combination strategies.

About Durvalumab:
Durvalumab, a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumor’s immune-evading tactics and inducing an immune response.

As part of a broad development program, durvalumab is being investigated as monotherapy and in combination with IO, small molecules, and chemotherapies across a range of tumors and stages of disease.

About Cetuximab:
Cetuximab is an anti-EGFR monoclonal antibody blocking oncogenic signaling and inducing Fcγ receptor-mediated antibody dependent cellular cytotoxicity (ADCC). NK cells mediate cetuximab-induced ADCC against SCCHN. Genetic and preclinical experiments suggest that ADCC can be enhanced by NK-stimulators.

The activity of cetuximab single agent in R/M SCCHN is limited with a 12.6% ORR, a median PFS of 2.3 months and a median OS of 5.8 months (Vermorken et al, JCO 2007).

On October 1, 2019 ORPHELIA Pharma, a French biopharmaceutical company dedicated to the development and marketing of paediatric drugs in the fields of oncology and neurology, reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the issuance of a marketing authorization for Ivozall (Press release, ORPHELIA Pharma, OCT 1, 2019, View Source [SID1234539964]).

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Ivozall is a solution for infusion containing 1 mg/ml clofarabine and supplied in 20 ml-vials. Clofarabine is an essential medicine for the treatment of relapsed or refractory Acute Lymphoblastic Leukaemia (ALL) in children. Ivozall will be the first generic form of clofarabine to be authorised under the European centralized procedure.

« We are particularly pleased with this decision which comes after continuous efforts of our company together with our partners », comments Jeremy Bastid, Chief Development Officer of ORPHELIA Pharma. « This positive opinion is a key milestone in the process of making Ivozall, our first medicinal product in oncology, available to the paediatric community ».

« The CHMP has acknowledged the interest of Ivozall in improving health of children with ALL. We are eagerly awaiting the marketing authorisation expected for November 2019 », highlights Hugues Bienaymé, General Manager of ORPHELIA Pharma. « We anticipate to make Ivozall available to the hospital centres treating ALL patients in some countries from February 2020 », added Gilles Alberici, Chairman of ORPHELIA Pharma. « Other countries will be handled by ORPHELIA distributors, to be selected in the course of 2020 ».

About Acute Lymphoblastic Leukaemia

Acute Lymphoblastic Leukaemia is a cancer associated with the uncontrolled proliferation of lymphoblasts that invade the bone marrow. The disease progresses rapidly and aggressively and requires immediate treatment. ALL is a rare disease, with around 7,000 people diagnosed each year in Europe. The majority of ALL cases occurs in children. Although rare, ALL is the most common type of childhood cancer. Clofarabine is indicated for the treatment of ALL in paediatric patients who have relapsed or are refractory after receiving at least two prior regimens and where there is no other treatment option anticipated to result in a durable response.