On September 9, 2019 Mateon Therapeutics Inc. (OTCQB:MATN), reported that it has executed agreements with WideTrial Inc. for an Expanded Access program (EAP) in pancreatic cancer (Press release, Mateon Therapeutics, SEP 9, 2019, View Source [SID1234539377]). Using WideTrial’s novel platform, the investigational therapeutic OT-101 will be made available for elective treatment-use to patients who do not meet the inclusion criteria of OT-101 research trials. The partnership may also support Expanded Access for OT-101 in additional patients with advanced solid tumors, excluding brain cancers (AA, GBM, and other gliomas). Separately, the companies executed data access agreements to support the development of Mateon’s AI/Blockchain technologies with WideTrial’s data assets in cancer and other therapeutic areas.

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OT-101 is a first-in-class RNA therapeutic targeting TGF beta and is the lead immune-oncology drug candidate of Oncotelic, a wholly owned subsidiary of Mateon Therapeutics Inc.. The investigational drug exhibited single-agent activity in relapsed/refractory cancer patients during multiple Phase 2 clinical trials.

Like research trials, cohort Expanded Access programs (EAPs) are centrally monitored trials that enroll patients at designated sites under a single protocol. They differ from research trials in that their primary objective is to provide the option of treatment-use to patients who cannot take part in the product’s research trials.

"This Expanded Access program will allow us to meet the spirit of clinical trial inclusivity, as described in the 2017 FDA Reauthorization Act. We are pleased to have found a viable way to accommodate greater numbers of patients in need and the doctors who seek to treat them," said Dr. Vuong Trieu, Chairman and CEO of Mateon Therapeutics Inc.. "Though the primary objective is treatment, we intend to utilize generated data to improve the power and targeting of future research trials."

"The PointR platform applies cutting edge algorithms to clinical datasets and could be used to quickly and cost-effectively identify the best therapy tailored fit to a single individual. The ability to access EAP data is helpful to the development of this platform" said Saran Saund, CEO of PointR Data, which is becoming a wholly owned subsidiary of Mateon Therapeutics Inc.. "We are thrilled at the opportunity of vertically integrating artificial intelligence and drug development capabilities under one roof to quickly identify promising new therapeutic opportunities for various diseases and to deliver compelling business value."

"We built WideTrial to solve the economic and operational barriers that drug developers face with Expanded Access," said Jess Rabourn, CEO of WideTrial. "The new platform enables larger numbers of gravely ill patients to choose to try investigational medicines under a properly designed protocol. Although treatment is the primary objective, EAP sponsors can learn a lot from patients’ experiences in these programs."

On September 9, 2019 Phio Pharmaceuticals Corp. (NASDAQ: PHIO), a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (sd-rxRNA) therapeutic platform, reported that it has entered into a research collaboration with Carisma Therapeutics to evaluate the potential of Phio’s self-delivering RNAi compounds to synergistically modify Carisma’s chimeric antigen receptor macrophages (CAR-M) (Press release, Phio Pharmaceuticals, SEP 9, 2019, View Source [SID1234539376]). Silencing of key genes using sd-rxRNA compounds may enhance the immune function of these cells as a novel adoptive cell therapy for use in cancer treatment.

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"Overcoming local tumor immunosuppression remains a significant challenge in the treatment of cancer," said Dr. John A. Barrett, Chief Development Officer of Phio Pharmaceuticals. "We have established collaborations with several companies and academic institutions to validate our technology’s ability to improve the activity of T cells, TILS, NK cells and dendritic cells towards tumors. Macrophages are sentinel cells of the innate immune system that robustly accumulate in most solid tumors. Combining Phio’s gene silencing technology with Carisma’s CAR-M technology has the potential to enhance aspects of macrophage anti-tumor activity and may further tip the scale in favor of an immunostimulatory phenotype and enhance tumor cell killing. We believe we can leverage both technologies to turn cold tumors hot and ultimately improve outcomes for patients."

Dr. Gerrit Dispersyn, Phio Pharmaceuticals’ President and CEO stated "We are very excited to work with the Carisma Therapeutics team, which represents our first collaboration addressing macrophages utility as an immunotherapeutic. By combining Carisma’s unique approach to adoptive cell therapy using CAR macrophages with our self-delivering RNAi technology, we expect to demonstrate potential synergies between our platforms that could enable us to bring new and improved forms of adoptive cell therapy to patients in the future. Our overall strategy in this setting is to generate robust data that validate our platform for the weaponization of a broad range of immune cells against tumors in order to generate future partnerships and build shareholder value."

"Metastatic solid tumors have been an intractable challenge for engineered cell therapies. Our platform technology, based on the genetically engineered macrophage, has a unique opportunity to provide benefit in this disease state," said Dr. Michael Klichinsky, co-Founder and Vice President of Discovery at Carisma. "We are excited to work with Phio to evaluate sd-rxRNA mediated silencing of genes that have the potential to enhance macrophage immunotherapy."

On September 9, 2019 Altimmune, Inc. (Nasdaq: ALT), a clinical-stage biopharmaceutical company, reported it has appointed M. Scott Harris, M.D. as Chief Medical Officer (Press release, Altimmune, SEP 9, 2019, View Source [SID1234539375]). Dr. Harris is succeeding Dr. Sybil Tasker, who resigned June 30, 2019 to continue her professional focus on infectious diseases.

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"Dr. Harris is a seasoned medical professional with extensive experience in hepatology and gastroenterology and broad expertise in managing clinical trials from early stage development through successful Phase 3 trials. He has led multidisciplinary forums on drug development and clinical trial design at national and international scientific meetings, and fostered collaborations between professional medical societies and the FDA. We are thrilled that a candidate of Dr. Harris’ caliber is joining the Altimmune team," said Vipin K. Garg, Ph.D., President and Chief Executive Officer. "We expect his clinical leadership to be pivotal to our success, and his appointment is timely as we are currently designing our ALT-801, HepTcell, and NasoShield clinical trials."

Dr. Harris added, "I am delighted to be joining Altimmune, and was attracted to the opportunity based on the Company’s pipeline and strong balance sheet. My background in liver and GI drug development especially complements Altimmune’s liver disease portfolio and I look forward to guiding these programs through the clinic. This is an exciting time to join Altimmune."

Dr. Harris is an accomplished drug development scientist who has led numerous global clinical studies and programs in GI and liver diseases. Previously, he was co-founder and Chief Medical Officer of Lyric Pharmaceuticals, helping raise a $21 million Series A round in 2014. He has also served as Chief Medical Officer of Avaxia Biologics, interim Chief Medical Officer of Tranzyme Pharma, and Chief Medical Officer of Ocera Therapeutics. Dr. Harris was also Chief Medical Officer and Vice President of Clinical Affairs at Napo Pharmaceuticals where he authored the pivotal clinical study that led to the approval of crofelemer (Mytesi), the first Phase 2/3 adaptive trial design resulting in a drug approval. Earlier in his career he held senior roles in global clinical development and medical affairs at Otsuka Pharmaceuticals and Abbott. He sits on the faculty of Georgetown University School of Medicine as an Adjunct Professor, where he directs a course on drug development under a grant from the NIH. Dr. Harris has been a consultant on third-world drug development for the Bill and Melinda Gates Foundation and a speaker at national and international forums on drug development. Dr. Harris has an M.D. from Harvard Medical School and an MS in Administrative Medicine and Population Health from the University of Wisconsin Medical School. His post-graduate training includes residencies at John Hopkins Hospital and the University of Pennsylvania, and a Gastroenterology and Hepatology Fellowship at the Yale University School of Medicine.

On September 9, 2019 PharmaMar (MSE:PHM) reported new data on lurbinectedin during the World Conference on Lung Cancer (WCLC), which is taking place from 7th to 10th September in Barcelona (Press release, PharmaMar, SEP 9, 2019, View Source [SID1234539374]). The Conference, organized by the International Association for the Study of Lung Cancer (IASLC), brings together the world’s leading experts on this pathology and presents the latest advances in its treatment.

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At this conference, PharmaMar presented two posters on lurbinectedin for the treatment of Small Cell Lung Cancer (SCLC).

The first of them evaluates new combinations with lurbinectedin for the treatment of this type of tumor. The poster entitled "Lurbinectedin (L) Combined with Paclitaxel (P) or Irinotecan (I) in Relapsed SCLC. Results from Two Phase Ib Trials (Abstract 1588)" shows the results of a Phase Ib trial in which combinations of lurbinectedin with paclitaxel or irinotecan were evaluated in patients with relapsed SCLC. Both combinations have shown similar activity and a predictable and manageable safety profile. The combination of lurbinectedin and irinotecan has shown encouraging activity in the third line treatment of patients. Also of interest, the combination of lurbinectedin and paclitaxel has shown higher activity in resistant patients (CTFI<90 days – patients for whom time from the last dose of first-line chemotherapy to the occurrence of progressive disease is less than 90 days).
These results warrant further evaluation of the combinations of lurbinectedin with paclitaxel or irinotecan. The expansion cohort of the irinotecan combination is already ongoing.

The second poster, entitled "Antitumor Activity of Single Agent Lurbinectedin in Patients with Relapsed SCLC Occurring ≥30 Days After Last Platinum Dose (Abstract 1710)" shows data from SCLC cohort of the Phase II Basket trial of lurbinectedin as a single agent, (presented in an oral session at the last ASCO (Free ASCO Whitepaper) Congress). Data are shown for the subset of 84 patients with a CTFI≥30 (time from the last dose of first-line chemotherapy to the occurrence of progressive disease is longer than or equal to 30 days). In this group of patients, the Overall Response Rate (ORR) was 40.5%. For the resistant patients with a CTFI of 30-89 days, the ORR was 29.2%, for whom no currently approved treatment exists. For the 60 patients that were sensitive (CTFI≥90 days; patients for whom time from the last dose of first-line chemotherapy to the occurrence of progressive disease is longer than or equal to 90 days), the ORR was 45%.

As for the safety of the compound in this group of patients, lurbinectedin has shown a safety profile that was acceptable and well tolerated. The most common treatment-related adverse effect has been neutropenia, and no unexpected toxicities have been observed.

During the Congress, Dr. Camilla L. Christensen, from Harvard University, will present in an oral session on transcription as a target in the treatment of SCLC, where, among others, the mechanism of action of lurbinectedin will be discussed. Lurbinectedin is a selective inhibitor of the oncogenic transcription programs on which many tumors are particularly dependent.

On September 9, 2019 AstraZeneca reported detailed results from the Phase III CASPIAN trial, showing Imfinzi (durvalumab) significantly improved overall survival (OS) in patients with previously-untreated extensive-stage small cell lung cancer (SCLC) (Press release, AstraZeneca, SEP 9, 2019, View Source [SID1234539373]).

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Imfinzi in combination with four cycles of standard-of-care (SoC) chemotherapy (etoposide with either cisplatin or carboplatin) demonstrated a statistically-significant and clinically-meaningful improvement in OS vs. SoC consisting of up to six cycles of chemotherapy and optional prophylactic cranial irradiation (PCI).

The risk of death was reduced by 27% (equal to a hazard ratio of 0.73), with median OS of 13.0 months for Imfinzi plus chemotherapy vs. 10.3 months for SoC. Results showed a prolonged OS benefit with an estimated 33.9% of patients alive at 18 months following treatment with Imfinzi plus chemotherapy vs. 24.7% of patients following SoC.

Across all efficacy endpoints, benefits were observed in patients treated with Imfinzi plus chemotherapy vs. SoC. Results showed a significantly higher progression-free survival (PFS) rate at 12 months (17.5% vs. 4.7%), a 10.3% increase in confirmed objective response rate (ORR) (67.9% vs. 57.6%), and improved duration of response (DOR) at 12 months (22.7% vs. 6.3%).

The results were presented at the Presidential Symposium of the IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer in Barcelona, Spain.

José Baselga, Executive Vice President, Oncology R&D said: "We are encouraged to see more than a third of small cell lung cancer patients treated with Imfinzi plus chemotherapy alive at the 18-month landmark, which is remarkable given the aggressive nature of the disease. It is also noteworthy that these results may enable physicians to choose Imfinzi in combination with either cisplatin or carboplatin chemotherapy backbones. We look forward to working with regulatory authorities to bring Imfinzi to patients with small cell lung cancer around the world as soon as possible."

Luis Paz-Ares, MD, Ph.D., Chair, Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid, Spain and principal investigator in the Phase III CASPIAN trial said: "Patients have had limited treatment options for small cell lung cancer, a devastating disease where the five-year survival rate has been as low as 6%. The significant survival benefit demonstrated with Imfinzi combined with only four cycles of a choice of chemotherapy compared to a robust control arm, provides evidence and hope of a new treatment option for these patients."

SCLC is an aggressive, fast-growing cancer that recurs and progresses rapidly despite initial response to platinum-based chemotherapy.1

i Etoposide plus investigator choice of cisplatin or carboplatin chemotherapy.

ii The data cut-off date for analysis of OS, PFS and ORR was 11 March 2019.

iii PFS was not formally tested for statistical significance.

iv Confirmed responses according to investigator assessment per RECIST v1.1.

The safety and tolerability of Imfinzi in combination with SoC etoposide and platinum-based chemotherapy was consistent with previous trials. Results showed that 61.5% of patients experienced a Grade 3 or 4 AE with Imfinzi plus SoC (all causes) vs. 62.4% with SoC, and patients discontinuing treatment due to AEs were similar between arms (9.4% vs. 9.4%).

Imfinzi is also being tested following concurrent chemoradiation therapy in limited-stage SCLC in the Phase III ADRIATIC trial.

Imfinzi is approved in the curative-intent setting of unresectable, Stage III non-small cell lung cancer after chemoradiotherapy in 49 countries, including the US, Japan and across the EU, based on the Phase III PACIFIC trial.

About CASPIAN

The CASPIAN trial is a randomised, open-label, multi-centre, global, Phase III trial in the 1st-line treatment of patients with extensive-stage SCLC. The trial compared Imfinzi in combination with etoposide and either cisplatin or carboplatin chemotherapy, or Imfinzi, tremelimumab and chemotherapy vs. chemotherapy alone. In the experimental arms, patients were treated with up to four cycles of chemotherapy. In comparison, the control arm allowed up to six cycles of chemotherapy and optional PCI. The trial will continue to the final analysis of OS for the combination of Imfinzi, tremelimumab and chemotherapy.

The trial is being conducted in more than 200 centres across 22 countries, including in the US, Europe, South America, Asia and the Middle East. The primary endpoint is OS.

About small cell lung cancer

Lung cancer is the leading cause of cancer death among both men and women and accounts for about one-fifth of all cancer deaths.2 Lung cancer is broadly split into NSCLC and SCLC, with about 15% classified as SCLC.3 About three quarters of SCLC patients are diagnosed with extensive-stage disease, in which the cancer has spread widely through the lung or to other parts of the body. Prognosis is particularly poor, as only 6% of all SCLC patients will be alive five years after diagnosis.4

About Imfinzi

Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is also approved for previously-treated patients with advanced bladder cancer in 10 countries, including the US.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, small cell lung cancer, bladder cancer, head and neck cancer, liver cancer, cervical cancer, biliary tract cancer and other solid tumours.

About AstraZeneca in lung cancer

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage clinical development for the treatment of different forms of lung cancer spanning several stages of disease, lines of therapy and modes of action. We aim to address the unmet needs of patients with EGFR-mutated tumours as a genetic driver of disease, which occur in 10-15% of NSCLC patients in the US and EU and 30-40% of NSCLC patients in Asia, with our approved medicines Iressa (gefitinib) and Tagrisso (osimertinib), and ongoing Phase III trials ADAURA, LAURA, FLAURA and FLAURA2 as well as the Phase II combination trials SAVANNAH and ORCHARD.5-7

Our extensive late-stage Immuno-Oncology programme focuses on lung cancer patients without a targetable genetic mutation which represents approximately three-quarters of all patients with lung cancer.8 Imfinzi (durvalumab), an anti-PDL1 antibody, is in development for patients with advanced disease (Phase III trials POSEIDON, PEARL, and CASPIAN) and for patients in earlier stages of disease including potentially-curative settings (Phase III trials AEGEAN, PACIFIC-2, ADRIATIC, ADJUVANT BR.31, PACIFIC-4, and PACIFIC-5) both as monotherapy and in combination with tremelimumab and/or chemotherapy.

About AstraZeneca’s approach to Immuno-Oncology (IO)

IO is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. Our IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. We believe that IO-based therapies offer the potential for life-changing cancer treatments for the clear majority of patients.

We are pursuing a comprehensive clinical-trial programme that includes Imfinzi (anti-PDL1) as monotherapy and in combination with tremelimumab (anti-CTLA4) in multiple tumour types, stages of disease, and lines of therapy, using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine our IO portfolio with radiation, chemotherapy, small targeted molecules from across our Oncology pipeline, and from our research partners, may provide new treatment options across a broad range of tumours.

About AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca’s main capabilities, the Company is actively pursuing innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by the investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.