On July 31, 2017 AstraZeneca and MedImmune, its global biologics research and development arm, reported that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for Imfinzi (durvalumab) for the treatment of patients with locally-advanced, unresectable non-small cell lung cancer (NSCLC) whose disease has not progressed following platinum-based chemoradiation therapy (Press release, AstraZeneca, JUL 31, 2017, View Source [SID1234519937]).

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Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "For patients who have not progressed following chemoradiation therapy the only current option is active monitoring. Unfortunately, for the majority of patients, their cancer will progress to metastatic disease, typically within 12 months. Imfinzi is the first immuno-oncology medicine to show a clinically-significant benefit in this earlier, non-metastatic setting, so following the Breakthrough Designation we hope to bring it to patients as soon as possible."

The Breakthrough Therapy Designation is designed to expedite the development and regulatory review of new medicines that are intended to treat a serious condition and that have shown encouraging early clinical results, which demonstrate substantial improvement on a clinically-significant endpoint over available medicines and when there is significant unmet medical need.

The Breakthrough Therapy Designation for Imfinzi was granted on the basis of interim results from the Phase III PACIFIC trial, a randomised, double-blinded, placebo-controlled multi-centre trial of Imfinzi as sequential treatment in patients with locally-advanced, unresectable (Stage III) NSCLC who had not progressed following standard platinum-based chemotherapy concurrent with radiation therapy. This achievement follows the recent accelerated approval from the US FDA for Imfinzi in previously-treated patients with advanced bladder cancer, and is the fourth Breakthrough Therapy Designation AstraZeneca has received from the FDA for a New Oncology cancer medicine over the past three years, the second for Imfinzi.

Data from the PACIFIC trial have been submitted for presentation at a forthcoming medical meeting.

Imfinzi is also being tested in the adjuvant NSCLC setting in the ADJUVANT Phase III trial. In the Stage IV 1st-line setting for patients with advanced NSCLC, Imfinzi as monotherapy and in combination with tremelimumab, an anti-CTLA4, is being tested in the MYSTIC, NEPTUNE, and PEARL Phase III trials. The POSEIDON trial is evaluating Imfinzi with and without tremelimumab in combination with chemotherapy.

About PACIFIC

The PACIFIC trial is a randomised, double-blinded, placebo-controlled multi-centre trial of Imfinzi as sequential treatment in unselected patients with locally-advanced, unresectable (Stage III) NSCLC who have not progressed following platinum-based chemotherapy concurrent with radiation therapy.

The trial is being conducted in 235 centres across 26 countries, including the US, Canada, Europe, South and Central America, Japan, Korea, Taiwan, South Africa and Australia. The primary endpoints of the trial are PFS and OS, and secondary endpoints include landmark PFS and OS, objective response rate and duration of response.

About Imfinzi

Imfinzi (durvalumab), a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumour’s immune-evading tactics and inducing an immune response.

Imfinzi continues to be studied in multiple monotherapy trials and combination trials with tremelimumab and other potential new medicines in immuno-oncology. Imfinzi is being assessed in Phase III trials as a monotherapy in various stages of NSCLC, in small-cell lung cancer (SCLC), in metastatic urothelial cancer (mUC) and in head and neck squamous cell carcinoma (HNSCC). The combination of Imfinzi and tremelimumab is being assessed in Phase III trials in NSCLC, SCLC, mUC and HNSCC and in Phase I/II trials in hepatocellular carcinoma (HCC) and haematological malignancies.

About Locally-Advanced (Stage III) NSCLC

Stage III lung cancer is divided into two stages (IIIA and IIIB), which are defined by how much the cancer has spread locally and the possibility of surgery. This differentiates it from Stage IV disease, when the cancer has metastasised to other organs.

Stage III lung cancer represents approximately one third of NSCLC incidence and was estimated to affect around 100,000 patients in the G7 countries in 2016. About half of these patients have tumours that are unresectable. The current standard of care is chemotherapy and radiation followed by active surveillance to monitor for progression. The prognosis remains poor and long-term survival rates are low.

On July 31, 2017 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported that the company has entered into a definitive agreement to purchase the Bruton’s tyrosine kinase (BTK) inhibitor program from Redx Pharma Plc (Press release, Loxo Oncology, JUL 31, 2017, View Source [SID1234519934]). The lead candidate from this program is expected to enter clinical development in 2018.

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"We are excited to add another program to our pipeline that so nicely aligns with our larger strategic vision and capabilities," said Jacob Van Naarden, chief business officer of Loxo Oncology. "The Redx team has created novel chemical matter that selectively and reversibly inhibits BTK, a validated molecular target across numerous B-cell leukemias and lymphomas. It is our belief that the widespread use of covalent BTK inhibitors, such as ibrutinib, will increasingly drive acquired resistance through a mutational event in BTK called C481S, leading to a group of relapsing patients in need of new therapies. Our work suggests that a highly selective, reversible BTK inhibitor can address this emerging unmet need in patients whose disease has progressed on a covalent BTK inhibitor. The development of a highly selective compound in a genetically-defined population is a Loxo Oncology core competency."

Under the terms of the agreement, Loxo Oncology has made a $40M payment to Redx Pharma Plc for the full acquisition of the BTK discovery program, including lead candidate LOXO-305 (formerly RXC005). Loxo Oncology is not subject to milestone or royalty obligations.

LOXO-305 was designed to reversibly bind BTK and preserve activity in the presence of the C481S acquired resistance mutation. Additionally, it was designed to avoid off-target kinases that have complicated the development of both covalent and reversible BTK inhibitors, such as EGFR, BMX, TEC, ITK, BLK, LCK and SRC. LOXO-305 will be entering studies in the coming months to enable submission of an Investigational New Drug (IND) application in 2018.

On July 28, 2017 CytRx Corporation (NASDAQ: CYTR), a biopharmaceutical research and development company specializing in oncology, reported that it has entered into a global strategic license with NantCell, Inc., for the exclusive rights to develop and commercialize aldoxorubicin for all indications (Press release, CytRx, JUL 28, 2017, View Source [SID1234519933]). NantCell, a private subsidiary of NantWorks, LLC, is a clinical stage immuno-oncology company focused on developing novel molecularly targeted therapeutics including antibody, T-cell and NK cell based treatments for patients with cancer.

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"We are excited to forge this new relationship with NantCell. They are committed not just to bringing aldoxorubicin to the market for patients with soft tissue sarcomas, but to expand aldoxorubicin’s potential use in combination with both immuno-oncology and cell based therapies to better serve patients suffering from cancer," said Steven A. Kriegsman, CytRx’s Chairman and Chief Executive Officer. "This license and strategic investment will put aldoxorubicin in the hands of a committed partner who pioneered the development of albumin based chemotherapeutics, and will allow CytRx to continue to create new ultra-high potency drug candidates based on our LADR technology platform. Aldoxorubicin will clearly benefit from the first-hand experience of the NantCell management team led by Dr. Patrick Soon-Shiong, who developed and gained regulatory approval under a 505(b)(2) pathway and commercialized Abraxane, an albumin-mediated cytotoxic agent which currently grosses approximately $1 billion in annual sales."

"Aldoxorubicin’s distinct profile makes it the first anthracycline to allow for continuous dosing without increasing cardiac toxicity which would be beneficial for the 17 indications for which doxorubicin is currently approved and other indications where it could provide benefit," stated Dr. Soon-Shiong, NantCell’s Chairman and Chief Executive Officer. "We aim to rapidly incorporate aldoxorubicin into multiple treatment protocols for major tumor types like breast and brain cancers as well as sarcomas."

Under the terms of the license agreement, NantCell made a strategic investment by purchasing $13 million of CytRx common stock at $1.10 per share, representing approximately a 92% premium to CytRx’s most recent market price. CytRx is entitled to receive up to an additional $343 million in milestone payments related to regulatory approvals and commercial milestones for aldoxorubicin. In addition, CytRx will receive increasing double-digit royalties for sales of aldoxorubicin for soft tissue sarcomas and mid to high single digit royalties for all other indications. NantCell will be responsible for all future development, manufacturing and commercialization expenses. CytRx also issued NantCell a warrant to purchase up to 3 million shares of common stock at $1.10 over the next 18 months.

Aldoxorubicin is a rationally-engineered cytotoxic which combines doxorubicin, a widely used chemotherapeutic agent, with a novel linker molecule that binds directly and specifically to circulating albumin, the most abundant protein in the bloodstream. Protein-hungry tumors concentrate albumin, which facilitates the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. Typically, doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Using this acid-sensitive linker technology, aldoxorubicin delivers greater doses of doxorubicin (3 ½ to 4 times). To date, there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of drug well in excess of 6,500 mg/m2 of doxorubicin equivalents. Aldoxorubicin is the first-ever single agent to show superiority over doxorubicin in a randomized clinical trial in first-line soft tissue sarcomas.

In addition, CytRx has amended its long-term loan facility and will make a payment of $5 million to the lender upon the closing of the exclusive global license and strategic investment for aldoxorubicin.

CytRx was represented by Skadden, Arps, Slate, Meagher & Flom LLP on the global license and strategic investment.