On September 24, 2018 Applied DNA Sciences Inc. (NASDAQ: APDN) ("Applied DNA" or the "Company") reported that LineaRx, Inc. ("LineaRx"), its wholly-owned subsidiary focused on next-generation biotherapeutics, has signed a Joint Development Agreement (the "Agreement") with Takis S.R.L. and Evvivax S.R.L. ("Takis/Evvivax"), biotechnology companies focused on the discovery and development of DNA based anti-cancer vaccines for the human and animal markets, respectively (Press release, Applied DNA Sciences, SEP 24, 2018, View Source [SID1234529732]).

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Under the terms of the Agreement, LineaRx and Takis/Evvivax will jointly develop linear DNA expression vectors for two of Takis/Evvivax’s anti-cancer vaccine candidates utilizing LineaRx’s linear DNA technology. Linear DNA amplicons carrying the DNA sequences for Takis/Evvivax vaccine candidates will be delivered to preclinical animal models via Takis/Evvivax’s proprietary electroporation technology. Antigen-specific immune responses aimed at achieving therapeutic effects will be studied.

The previously announced collaboration between the companies has already shown promise of yielding immunity in mice that were DNA-vaccinated against the human protein telomerase, which is over-expressed in more than 85% of all cancers.

Dr. Luigi Aurisicchio, CEO of Takis/Evvivax stated: "We are excited to co-develop linear DNA expression vectors for our DNA vaccine candidates with LineaRx. Initial data from the use of LineaRx’s amplicons in our vaccine candidates is promising. The advantages of linear DNA over plasmids would provide a clear market edge over plasmid-based DNA sources. We look forward to a mutually beneficial collaboration".

"This Agreement serves to validate LineaRx’s technology as critical and necessary to the field of biotherapeutics in its ability to deliver potentially powerful approaches to the treatments of chronic diseases," stated Dr. James Hayward, president and CEO of Applied DNA. "Takis/Evvivax are ideal partners of LineaRx given their innovative anti-cancer vaccine candidates for both humans and animals together with their expertise in preclinical animal models."

Dr. Hayward continued, "The use of PCR-produced linear DNA, as opposed to bacterially produced plasmids, is an innovative concept that provides the potential for increased patient safety, ease of manufacture and vaccine logistics, and reduced costs. Our know-how in the fields of bulk linear DNA production and in bioconjugate chemistry enable us to create novel and highly efficient expression vectors."

With their stability at room temperature, low risk of infection or secondary illness, and stability during transportation, DNA vaccines overcome many of the undesirable properties of conventional vaccines. The global DNA based human vaccine market is expected to grow at a CAGR of 55% and reach a value of $2.7 billion by 20191. The global veterinary vaccine market is expected to reach $20.6 billion by 20212, with DNA based animal vaccines gaining rapid market share.

Takis/Evvivax emerged from a Merck-supported research center in Rome and has relationships across Big Pharma (View Source). The companies have agreed to seek sponsorship for their work together.

On September 24, 2018 OncoMed Pharmaceuticals, Inc. (NASDAQ:OMED), a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer therapeutics, reported that the results of its Phase 1a study with single-agent navicixizumab in patients with refractory solid tumors were published in Investigational New Drugs (Press release, OncoMed, SEP 24, 2018, View Source [SID1234529672]). The results showed that 19 of the 66 patients with various types of refractory solid tumors had tumor shrinkage following treatment with navicixizumab. Notably, 3 of the 12 (25%) ovarian cancer patients treated in the trial achieved a partial response with single-agent navicixizumab therapy. Navicixizumab is a bispecific antibody that was designed to enhance the anti-tumor effect observed with inhibition of DLL4 or VEGF alone.

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"These study results demonstrate that navicixizumab has single-agent anti-tumor activity in several tumor types and is particularly active in heavily pretreated ovarian cancer, a cancer with limited treatment options," said John Lewicki, Ph.D., President and Chief Executive Officer of OncoMed. "We look forward to presenting interim data from our Phase 1b study, which is evaluating navicixizumab in combination with paclitaxel in patients with heavily pretreated platinum-resistant ovarian cancer at the upcoming European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) meeting."

This Phase 1a multicenter, open-label, dose-escalation trial enrolled sixty-six patients with previously treated solid tumors. The primary endpoint was to determine the maximum tolerated dose. Secondary endpoints included safety, pharmacokinetics, immunogenicity and antitumor activity.

The most commonly enrolled tumor types were ovarian (12), colorectal (11) and cancers of the breast, pancreas, uterus and endometrium (four patients of each). Four patients (three ovarian cancer and one uterine carcinosarcoma) had a partial response, and 17 patients had stable disease. There were 19 patients that had a reduction in the size of their target lesions, including seven patients with ovarian cancer. Six of these seven ovarian cancer patients had prior bevacizumab. Four patients remained on study for >300 days and two of these patients were on study for >500 days. The most common drug related adverse events of any grade were hypertension (58%), headache (29%), fatigue (26%), and pulmonary hypertension (18%). Infusion reactions associated with anti-drug antibodies impacting drug exposure occurred in 11% of patients. The maximum tolerated dose for navicixizumab was not determined based on protocol-defined criteria, but doses of 3-4 mg/kg once every 2 weeks were chosen for the subsequent Phase 1b studies.

A Phase 1b multicenter, open-label, dose-escalation and expansion trial of navicixizumab in combination with paclitaxel in patients with platinum-resistant ovarian cancer who have previously received bevacizumab and/or have failed at least two prior therapies is ongoing. Interim study results will be presented in a poster presentation on October 20, 2018 at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) meeting to be held in Munich, Germany.

About Navicixizumab
OncoMed’s anti-DLL4/VEGF bispecific antibody, navicixizumab, is designed to inhibit the function of both DLL4 and VEGF and thereby induce potent anti-tumor responses while mitigating certain angiogenic-related toxicities. Navicixizumab was developed utilizing OncoMed’s BiMAb bispecific platform technology, which enables the design of bispecific antibodies comparable to traditional monoclonal antibodies but possessing dual target-binding specificity. In preclinical studies, navicixizumab demonstrated robust in vivo anti-tumor efficacy across a range of solid tumor xenografts, including colon, ovarian, lung and pancreatic cancers, among others. Further, in preclinical studies dual inhibition of DLL4 and VEGF appeared to exhibit synergistic anti-tumor activity at doses where blockade of either target alone elicited sub-optimal activity.

On September 24, 2018 OncoMed Pharmaceuticals, Inc. (NASDAQ:OMED), a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer therapeutics, reported that John Lewicki, Ph.D., President and Chief Executive Officer of OncoMed, will present a corporate update at the 2018 Cantor Global Healthcare Conference in New York, NY on Monday, October 1, 2018 at 5:15 pm Eastern Time (Press release, OncoMed, SEP 24, 2018, View Source [SID1234529671]).

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To access the live webcast and subsequent archived recording of this presentation, or other company presentations, please visit OncoMed’s website at www.oncomed.com/invest/events.cfm. A replay will be available for 30 days following the date of the event.

On September 24, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported results from the Phase III IMpower132 study of Tecentriq (atezolizumab) plus pemetrexed and platinum-based chemotherapy (cisplatin or carboplatin) for the initial (first-line) treatment of people with non-squamous, non-small cell lung cancer (NSCLC) (Press release, Hoffmann-La Roche, SEP 24, 2018, View Source [SID1234529662]). This interim analysis showed that Tecentriq and chemotherapy reduced the risk of disease worsening or death (progression-free survival, PFS) by 40% compared with chemotherapy alone (PFS=7.6 versus 5.2 months; hazard ratio [HR]=0.60, 95% CI: 0.49-0.72; p<0.0001).1 While a numerical improvement of 4.5 months for the co-primary endpoint of overall survival (OS) was observed, at this interim analysis statistical significance has not yet been met (median OS=18.1 versus 13.6 months; HR=0.81, 95% CI: 0.64-1.03; p=0.0797). The study will continue as planned, with final OS results expected next year. Safety for the Tecentriq and chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination.

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"This is our third Phase III trial in non-squamous non-small cell lung cancer demonstrating that a Tecentriq -based regimen can help reduce the risk of disease progression for people living with this disease," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We will discuss these results with health authorities globally."

Data will be presented at the International Association for the Study of Lung Cancer (IASLC) 2018 World Conference on Lung Cancer (WCLC) on Monday 24 September at 14:35-14:45 EDT (Abstract OA05.07 Oral) and featured in the official WCLC press conference at 09:45-10:30 EDT.

About the IMpower132 study
IMpower132 is a Phase III, open-label, randomised study evaluating the efficacy and safety of Tecentriq plus chemotherapy (cisplatin or carboplatin and pemetrexed) versus chemotherapy alone in chemotherapy-naïve patients with NSCLC. The study enrolled 578 people who were randomised equally (1:1) to receive:

Tecentriq in combination with cisplatin or carboplatin and pemetrexed (Arm A),
or Cisplatin or carboplatin and pemetrexed (Arm B, control arm)
During the treatment-induction phase, people received Tecentriq, pemetrexed and investigator’s choice of either cisplatin or carboplatin on Day 1 of every three weeks for a dosing period of four or six cycles. People who experienced clinical benefit during the induction phase began maintenance therapy until disease progression.

The co-primary endpoints were:

PFS as determined by the investigator using RECIST v1.1
OS
IMpower132 met its PFS co-primary endpoint as per the study protocol. A summary of the results are included below:

Safety for the Tecentriq and chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination. Grade 3-4 treatment-related adverse events (AEs) were reported in 53.6 percent of people receiving Tecentriq plus chemotherapy compared to 39.1 percent of people receiving chemotherapy alone.

About NSCLC
Lung cancer is the leading cause of cancer death globally.2 Each year 1.76 million people die as a result of the disease; this translates into more than 4,800 deaths worldwide every day.2 Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.3 NSCLC comprises non-squamous and squamous-cell lung cancer, the squamous form of which is characterised by flat cells covering the airway surface when viewed under a microscope.3

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

Currently, Roche has eight Phase III lung cancer studies evaluating Tecentriq alone or in combination with other medicines.

Tecentriq is already approved in the European Union, United States and more than 70 countries for people with previously treated metastatic NSCLC and for certain types of untreated or previously treated metastatic urothelial carcinoma (mUC).

On September 24, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported results for its investigational medicine entrectinib, from an integrated analysis of the pivotal phase II STARTRK-2, phase I STARTRK-1 and phase I ALKA trials, which showed that entrectinib shrank tumours (objective response rate; ORR) in 77.4% of people with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) (Press release, Hoffmann-La Roche, SEP 24, 2018, View Source [SID1234529661]).1 In addition, entrectinib demonstrated a durable response of more than two years (duration of response [DoR] = 24.6 months).1 Importantly, entrectinib was shown to shrink tumours in more than half of people with cancer in the central nervous system (CNS) (intracranial ORR: 55.0%).1 The safety profile of entrectinib was consistent with that seen in previous analyses, and no new safety signals were identified.1 Based on the integrated analysis of these studies, Roche plans to submit these data to global health authorities.

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"These results show the potential of precision medicines to deliver tailored and effective treatment options for people with non-small cell lung cancer, including those whose tumours have spread to the central nervous system," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We are also investigating entrectinib in NTRK fusion-positive tumours across several different cancer types, and look forward to presenting those results in the near future."

ROS1 gene fusions have been identified in 1-2% of people with NSCLC.2 NSCLC is the most common type of lung cancer and accounts for 85% of all lung cancer diagnoses.3 Approximately 30-40% of people with ROS1-positive NSCLC have brain metastases at time of diagnosis.4

These ROS1 results will be presented at the 2018 World Conference on Lung Cancer (WCLC) in Toronto, Canada on Monday, 24 September 2018, from 10:30 – 10:40 a.m. EDT (Abstract 13903), and featured in the WCLC press programme on Monday, 24 September, from 9:45 – 10:30 a.m. EDT. Follow Roche on Twitter via @Roche and keep up to date with WCLC 2018 congress news and updates by using the hashtag #WCLC2018.

About the integrated analysis
The integrated analysis included data from 53 people with ROS1-activating gene fusions from the phase II STARTRK-2, phase I STARTRK-1 and phase I ALKA trials.1 The studies enrolled people across 15 countries and more than 150 clinical trial sites.1

STARTRK-2 is a phase II, global, multicentre, open-label basket study in people with solid tumours that harbour an NTRK1/2/3 or ROS1-positive gene fusion.5 The primary endpoint is ORR.5 Secondary outcome measures include DOR, time to response, clinical benefit rate, intracranial tumour response, progression-free survival (PFS), CNS PFS and overall survival (OS).5
STARTRK-1 is a phase I, multicentre, open-label dose escalation study of a daily continuous dosing schedule in people with solid tumours with NTRK1/2/3 or ROS1 gene fusions in the US and South Korea.6 The trial assessed the safety and tolerability of entrectinib via a standard dose escalation scheme and determined the recommended phase II dose.6
ALKA is a phase I, multicentre, open-label dose escalation study of an intermittent and continuous entrectinib dosing schedule in people with advanced or metastatic solid tumours with ROS1 gene fusions in Italy.7
Adverse events were consistent with previous data.1 The most commonly reported adverse events include those affecting the nervous system, as well as constipation, altered sense of taste (dysgeusia) and fatigue.1

About entrectinib
Entrectinib (RXDX-101) is an investigational, oral medicine in development for the treatment of locally advanced or metastatic solid tumours that harbour NTRK1/2/3 or ROS1 gene fusions. It is a selective, CNS-active tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRKA/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer.8,9 Entrectinib can block ROS1 and NTRK kinase activity and may result in the death of cancer cells with ROS1 or NTRK gene fusions.8,9 Entrectinib is being investigated across a range of solid tumour types, including non-small cell lung cancer, pancreatic cancer, sarcomas, thyroid cancer, salivary cancer, gastrointestinal stromal tumours (GIST) and cancers of unknown primary (CUP).5-7

Entrectinib has been granted Breakthrough Therapy Designation (BTD) by the US Food and Drug Administration (FDA); Priority Medicines (PRIME) designation by the European Medicines Agency (EMA); and Sakigake designation by the Japanese health authorities for the treatment of NTRK-positive, locally advanced or metastatic solid tumours in adult and pediatric patients who have either progressed following prior therapies or have no acceptable standard therapies.7

About ROS1-positive non-small cell lung cancer (NSCLC)
ROS1 is a tyrosine kinase, which plays a role in controlling how cells grow and proliferate. When a ROS1 gene fusion occurs, cancer cells grow and proliferate in an uncontrolled manner. Blocking this abnormal signalling can cause tumour cells to shrink or die.2

ROS1 gene fusions account for 1-2% of non-small-cell lung cancer (NSCLC).2 Lung cancer is the leading cause of cancer-related death across the world.10 Each year, more than one and a half million people die as a result of the disease globally, equating to more than 4,000 deaths every day.10 NSCLC is the most common type of lung cancer and accounts for 85% of all lung cancer diagnoses.3 While the ROS1 gene fusion can be found in any patient with NSCLC, young never-smokers with NSCLC have the highest incidence of ROS1 gene fusions.2