On March 17, 2020 AstraZeneca reported that High-level results from the final analysis of the Phase III CASPIAN trial showed Imfinzi (durvalumab) in combination with a choice of standard-of-care (SoC) chemotherapies confirmed a sustained, clinically meaningful overall survival (OS) benefit for patients with extensive-stage small cell lung cancer (ES-SCLC) treated in the 1st-line setting (Press release, AstraZeneca, MAR 17, 2020, View Source [SID1234555632]).

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In June 2019, the CASPIAN trial met one primary endpoint for Imfinzi plus SoC (etoposide and either carboplatin or cisplatin chemotherapy) by demonstrating a statistically significant and clinically meaningful improvement in OS versus SoC alone at a planned interim analysis.

The second experimental arm testing tremelimumab, an anti-CTLA4 monoclonal antibody, added to Imfinzi and SoC did not meet its primary endpoint of demonstrating a statistically significant improvement in OS in this analysis.

José Baselga, Executive Vice President, Oncology R&D, said: "We are pleased to see the sustained and meaningful survival benefit of Imfinzi for patients with small cell lung cancer after more than two years median follow up. We have already received the first global regulatory approval for Imfinzi with etoposide plus either carboplatin or cisplatin and remain on track for more approvals soon as we provide patients an important new 1st-line treatment option."

The safety and tolerability for Imfinzi and tremelimumab were consistent with the known safety profiles of these medicines. The data will be presented at a forthcoming medical meeting.

Imfinzi in combination with etoposide and either carboplatin or cisplatin is currently under regulatory review for the treatment of ES-SCLC in the 1st-line setting based on the Phase III CASPIAN trial in the US, EU and Japan. The US Food and Drug Administration has granted a Priority Review with a Prescription Drug User Fee Act date set for the first quarter of 2020.

As part of a broad development programme, Imfinzi is also being tested following concurrent chemoradiation therapy in patients with limited-stage SCLC in the Phase III ADRIATIC trial with data anticipated in 2021.

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.1 Lung cancer is broadly split into non-small cell lung cancer (NSCLC) and SCLC, with about 15% classified as SCLC.2 SCLC is a highly aggressive, fast-growing form of lung cancer that typically recurs and progresses rapidly despite initial response to chemotherapy.3,4 About two thirds 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.5 Prognosis is particularly poor, as only 6% of all SCLC patients will be alive five years after diagnosis.5

CASPIAN

CASPIAN is a randomised, open-label, multi-centre, global, Phase III trial in the 1st-line treatment of 805 patients with ES-SCLC. The trial compared Imfinzi in combination with etoposide and either carboplatin or cisplatin chemotherapy, or Imfinzi and chemotherapy with the addition of a second immunotherapy, tremelimumab, versus chemotherapy alone. In the experimental arms, patients were treated with four cycles of chemotherapy. In comparison, the control arm allowed up to six cycles of chemotherapy and optional prophylactic cranial irradiation. The trial was conducted in more than 200 centres across 23 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint was OS in each of the two experimental arms.

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 approved in the curative-intent setting of unresectable, Stage III NSCLC after chemoradiation therapy in the US, Japan, China, across the EU and in many other countries, based on the Phase III PACIFIC trial. Imfinzi recently received its first global approval for the 1st-line treatment of ES-SCLC in combination with SoC chemotherapy in Singapore. Imfinzi is also approved for previously treated patients with advanced bladder cancer in the US and a small number of other countries.

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, SCLC, bladder cancer, head and neck cancer, liver cancer, biliary tract cancer, cervical cancer and other solid tumours.

Tremelimumab

Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T cell activation, priming the immune response to cancer and fostering cancer cell death. Tremelimumab is being tested in a clinical trial programme in combination with Imfinzi in NSCLC, SCLC, bladder cancer, head and neck cancer and liver cancer.

AstraZeneca in lung cancer

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, 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 the approved medicines Iressa (gefitinib) and Tagrisso (osimertinib), and its ongoing Phase III trials ADAURA, LAURA, and FLAURA2.6-8 We are also committed to addressing tumour mechanisms of resistance through the ongoing Phase II trials SAVANNAH and ORCHARD which test Tagrisso in combination with savolitinib, a selective inhibitor of c-MET receptor tyrosine kinase, along with other potential new medicines. Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate is in development for metastatic non-squamous HER2-overexpressing or HER2-mutated NSCLC including trials in combination with other anticancer treatments.

An extensive late-stage Immuno-Oncology programme focuses on lung cancer patients without a targetable genetic mutation which represents up to three-quarters of all patients with lung cancer.9 Imfinzi, an anti-PDL1 antibody, is in development for patients with advanced disease (Phase III trials POSEIDON, and PEARL) and for patients in earlier stages of disease including potentially-curative settings (Phase III trials AEGEAN, ADJUVANT BR.31, PACIFIC-2, PACIFIC-4, PACIFIC-5, and ADRIATIC) both as monotherapy and in combination with tremelimumab and/or chemotherapy. Imfinzi is also in development in the Phase II combination trials NeoCOAST, COAST and HUDSON in combination with potential new medicines from the early-stage pipeline.

AstraZeneca’s approach to Immuno-Oncology (IO)

Immuno-oncology (IO) is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. The Company’s IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. AstraZeneca believes that IO-based therapies offer the potential for life-changing cancer treatments for the clear majority of patients.

The Company is pursuing a comprehensive clinical-trial programme that includes Imfinzi as a monotherapy and in combination with tremelimumab in multiple tumour types, stages of disease, and lines of therapy, and where relevant 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 the IO portfolio with radiation, chemotherapy, small targeted molecules from across AstraZeneca’s Oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

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 six new medicines 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.

On March 17, 2020 DiaMedica Therapeutics Inc. (Nasdaq: DMAC) reported that its fourth quarter 2019 financial results will be released after the markets close on Monday, March 23rd (Press release, DiaMedica, MAR 17, 2020, View Source [SID1234555650]). DiaMedica will host a live conference call on Tuesday, March 24th at 7:00 AM Central Time to discuss its business update and financial results.

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Conference Call details:

Date:

Tuesday, March 24, 2020

Time:

7:00 AM CT / 8:00 AM ET

Web access:

View Source

Dial In:

(844) 557-8483 (domestic)

(825) 312-2381 (international)

Conference ID:

9270458

Interested parties may access the conference call by dialing in or listening to the simultaneous webcast. Listeners should log on to the website or dial in 15 minutes prior to the call. The webcast will remain available for play back on our website, under investor events and presentations, following the earnings call and for 12 months thereafter. A telephonic replay of the conference call will be available until March 31, 2020, by dialing (800) 585-8367 (US Toll Free), (416) 621-4642 (International), replay passcode 9270458.

On March 17, 2020 Kitov Pharma Ltd. ("Kitov") (NASDAQ/TASE: KTOV), a clinical-stage company advancing first-in-class therapies to overcome tumor immune evasion and drug resistance, reported the closing of its previously announced public offering of 20,000,000 units at a price to the public of $0.30 per unit, for gross proceeds of $6.0 million, before deducting placement agent fees and other offering expenses payable by Kitov (Press release, Kitov Pharmaceuticals , MAR 17, 2020, View Source [SID1234555633]). Each unit contains one American Depositary Shares ("ADS") (or ADS equivalent) and one warrant to purchase one ADS. Each ADS represents one ordinary share, no par value, of Kitov. The ADSs (or ADS equivalents) and warrants included in the units were purchased together in the offering, but were issued separately and are immediately separable. The warrants have an exercise price of $0.325 per ADS and will be exercisable at any time after the date of issuance and will expire five years from the date of issuance.

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H.C. Wainwright & Co. acted as the exclusive placement agent for the offering.

Kitov intends to use the net proceeds of this offering to fund the development of its oncology drug candidates, acquisition of new assets and for general working capital purposes.

The offering was made under an effective registration statement on Form F-1 (File No. 333-235729) filed with the Securities and Exchange Commission (the "SEC") and declared effective on March 11, 2020. The offering was made only by means of a prospectus forming part of the effective registration statement. The final terms of the offering are disclosed in a final prospectus filed with the SEC and made available on the SEC’s website at www.sec.gov. Electronic copies of the final prospectus relating to the offering may also be obtained by contacting H.C. Wainwright & Co., 430 Park Avenue, New York, NY 10022, by telephone at (646) 975-6996 or by email at [email protected].

On March 17, 2020 OncoSec Medical Incorporated (NASDAQ:ONCS) (the "Company" or "OncoSec"), a company developing late-stage intratumoral cancer immunotherapies, reported the publication of positive TAVO monotherapy data in patients with metastatic melanoma in the Annals of Oncology (Press release, OncoSec Medical, MAR 17, 2020, View Source [SID1234555651]). The publication titled, "Intratumoral Delivery of Tavokinogene Telseplasmid Yields Systemic Immune Responses in Metastatic Melanoma Patients," features data previously highlighted at both American Association of Cancer Research (AACR) (Free AACR Whitepaper) and the Melanoma Bridge annual meetings. Annals of Oncology is the official publication of the European Society for Medical Oncology.

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The complete publication in Annals of Oncology is linked here and available on OncoSec’s website at View Source

The publication describes OncoSec’s study of patients with Stage III/IV melanoma who were treated intratumorally with plasmid encoding IL-12 (tavokinogene telseplasmid or TAVO), followed by electroporation on days 1, 5, and 8 every 90 days in the main study with additional patients treated in two exploration cohorts with alternative schedules. Correlative analyses for programmed death-ligand 1 (PD-L1), flow cytometry to assess changes in immune cell subsets and analysis of intratumoral immune-related gene expression were carried out on pre-and post-treatment samples from study patients, as well as from additional patients treated during exploration of additional dosing schedules beyond the pre-specified protocol dosing schedule. Response was measured by study-specific criteria to maximize detection of latent and potentially transient immune responses in patients with multiple skin lesions. Toxicities were graded by the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).

The objective overall response rate (ORR) was 35.7% in the main study, with a complete response (CR) rate of 17.9%. The median progression-free survival in the main study was 3.7 months while the median overall survival was not reached at a median follow up of 29.7 months. A total of 46% of patients in all cohorts having both injected and uninjected lesions experienced regression of at least one of these uninjected lesions and 25% had a net regression of all untreated lesions. Transient procedural pain (n = 24, 80%) and injection site reactions were the most commonly experienced adverse events.

Transcriptomic and immunohistochemistry analysis showed that immune activation and co-stimulatory transcripts were up-regulated, with an increase of adaptive immune resistance.

The publication concluded that intratumoral TAVO was well-tolerated and led to systemic immune responses in advanced melanoma patients. While tumor regression and increased immune infiltration were observed in treated as well as untreated/distal lesions, adaptive immune resistance limited the response.

"TAVO treatment appears to drive a change in the immune microenvironment, which results in an immune response to melanoma with minimal systemic toxicity. These data demonstrate that this in situ tumor vaccination strategy may be a safe and effective approach to inducing multiple sustained, productive changes in the immune microenvironment that would be too toxic using similar systemic agents and drive significant clinical results," concluded study co-author Adil Daud, M.D., Department of Medicine, University of California, San Francisco. "We look forward to continued evaluation of the TAVO approach as a monotherapy in future clinical trials."

TAVO is currently being evaluated as a combination therapy in multiple clinical trials, including KEYNOTE-695, a pivotal trial in late-stage anti-PD-1 checkpoint refractory metastatic melanoma, and two phase 2 trials, one for triple negative breast cancer (TNBC) and a second for head and neck cancer. TAVO enables the intratumoral delivery of DNA-based IL-12, a naturally occurring protein with immune-stimulating functions. OncoSec’s technology, which employs electroporation, is designed to produce a controlled, localized expression of IL-12 in the tumor microenvironment, enabling the immune system to target and attack tumors throughout the body. Results from recently completed clinical studies of TAVO have demonstrated a local immune response, and subsequently, a systemic effect as either a monotherapy or combination treatment approach.

"While our ongoing pivotal KEYNOTE-695 study is evaluating TAVO and KEYTRUDA combination therapy in late-stage checkpoint refractory metastatic melanoma patients and has begun to yield positive results, publication of monotherapy data with TAVO demonstrates its utility as a standalone treatment in this patient population," stated Christopher Twitty, Ph.D., OncoSec’s Chief Science Officer and a co-author of the publication. "The increase in adaptive resistance observed in the tumor microenvironment, in particular PD-L1, makes TAVO a particularly well-suited partner with anti-PD-1 checkpoint therapies. We are encouraged to see such a high response rate and will continue to evaluate TAVO’s utility as a monotherapy for metastatic melanoma."

Annals of Oncology is the latest among a presently growing volume of peer-reviewed journals to highlight the potential of TAVO as a novel immunotherapy. A recent publication in Cancer Immunology Research, linked here, also explored the mechanism of activation of systemic immunity in patients from the TAVO monotherapy study in metastatic melanoma patients. Additionally, Clinical Cancer Research featured TAVO monotherapy data in Merkel cell carcinoma on the cover of its February 2020 issue, linked here. You can find a list of all TAVO publications and scientific presentations at View Source

On March 17, 2020 Circle Pharma, Inc., a macrocycle drug discovery and development company focused on intractable cancer targets, reported that it has raised $45 million in a Series B financing (Press release, ShangPharma Innovation, MAR 17, 2020, View Source [SID1234555735]).

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The financing was led by The Column Group, with participation by Nextech Invest. All investors from the prior round – ShangPharma, LifeForce Capital, and the Berkeley Catalyst Fund – joined the financing.

In conjunction with the financing, Peter Svennilson, founder and managing partner of The Column Group, and Thilo Schroeder, Ph.D., partner at Nextech Invest were appointed to the board. John Josey, Ph.D., formerly President and CEO of Peloton Therapeutics, was appointed to the board as Chairman.

Proceeds from the investment will be used to advance Circle’s work to develop inhibitors of Cyclin A and Cyclin E, and to expand the company’s pipeline.

"We are delighted to have these premier life science investors supporting our Series B financing," said David J. Earp, J.D., Ph.D., Circle’s President and CEO. "With this strong backing, we will expand our team, drive our cyclin targeted programs towards the clinic, and apply our macrocycle platform to additional intractable targets."

Circle’s new board appointments:

Peter Svennilson is the founder and managing partner of The Column Group. He was the chairman of Aragon Pharmaceuticals (acquired by Johnson & Johnson) and Seragon Pharmaceuticals (acquired by Roche / Genentech) and was a board director of Gritstone Oncology, NGM Biopharmaceuticals, Immune Design and Constellation Pharmaceuticals. He is currently a board director of ORIC Pharmaceuticals, Ribon Therapeutics and Carmot Therapeutics.

Thilo Schroeder, Ph.D., is a partner at Nextech Invest, a Zurich-based oncology-focused investment firm. He previously served on the board of Peloton Therapeutics (acquired by Merck) and Blueprint Medicines. He is currently a board director at IDEAYA Biosciences, Revolution Medicines, PMV Pharma, Silverback Therapeutics and a board observer at Black Diamond Therapeutics.

John Josey, Ph.D., served as the President, Chief Executive Officer, and member of the Board of Directors at Peloton Therapeutics from 2013 until its acquisition by Merck in 2019. From 2011 to 2013, he was President and Chief Scientific Officer at Peloton, and from 1998 to 2011, Vice President of Discovery Chemistry at Array Pharma.

The continuing members of Circle’s board of directors are Walter H. Moos, Ph.D., CEO of ShangPharma Innovation and Managing Director of Pandect Bioventures, Matthew P. Jacobson, Ph.D., Circle Pharma co-founder, chair of the department of pharmaceutical chemistry at U.C. San Francisco and also co-founder of Global Blood Therapeutics, Relay Therapeutics and Cedilla Therapeutics, and David J. Earp, J.D., Ph.D., President and Chief Executive Officer of Circle Pharma.