On May 12, 2017 AstraZeneca and MedImmune, its global biologics research and development arm, reported positive results for the Phase III PACIFIC trial, a randomised, double-blinded, placebo-controlled multi-centre trial of Imfinzi (durvalumab) as sequential treatment in patients with locally-advanced, unresectable (Stage III) non-small cell lung cancer (NSCLC) who had not progressed following standard platinum-based chemotherapy concurrent with radiation therapy (Press release, AstraZeneca, MAY 12, 2017, View Source [SID1234519058]).

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A planned interim analysis conducted by an Independent Data Monitoring Committee (IDMC) concluded that the trial has already met a primary endpoint by showing statistically-significant and clinically-meaningful PFS, as assessed by blinded independent central review, in patients receiving Imfinzi compared to placebo. The results also demonstrate a favourable benefit/risk profile. The trial will also evaluate overall survival (OS), the other primary endpoint, which will be assessed in due course as specified by the protocol. AstraZeneca plans to submit the initial results from the PACIFIC trial for presentation at a forthcoming medical meeting.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "These are highly encouraging results for patients with locally-advanced lung cancer for whom surgery is not an option. We look forward to working with regulatory authorities around the world to bring Imfinzi to lung cancer patients as soon as possible. Alongside this, we continue to explore Imfinzi’s full potential as monotherapy as well as in combination with tremelimumab and other medicines in areas of continued unmet need across multiple types of cancer."

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[i]. About half of these patients have tumours that are unresectable. The prognosis remains poor and long-term survival rates are low.

AstraZeneca recently received accelerated approval from the US FDA for Imfinzi in previously treated patients with advanced bladder cancer. Imfinzi is also being tested in the 1st-line treatment of patients with NSCLC as monotherapy in the MYSTIC and PEARL Phase III trials. It is also being developed in combination with tremelimumab, a checkpoint inhibitor that targets CTLA-4, as part of the MYSTIC, NEPTUNE and POSEIDON Phase III trials.

[i] Kantar, other market research based on 2016 patient numbers; Globocan 2012. G7 countries include the US, Japan, Germany, the UK, France, Italy and Canada.

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, previously known as MEDI4736), 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 advance in multiple monotherapy trials and combination trials with tremelimumab and other potential new medicines in IO. Imfinzi is being assessed in Phase III trials as a monotherapy in various stages of NSCLC, in small-cell lung cancer (SCLC), in urothelial bladder cancer and in head and neck squamous cell carcinoma (HNSCC). The combination of Imfinzi and tremelimumab is being assessed in Phase III trials in urothelial bladder cancer, NSCLC, SCLC and HNSCC and in Phase I/II trials in gastric cancer, pancreatic cancer, hepatocellular carcinoma and haematological malignancies.

About AstraZeneca in NSCLC
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths and more than breast, prostate and colorectal cancers combined.

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage clinical development for the treatment of NSCLC across all stages of disease and lines of therapy. We aim to address unmet needs of patients with EGFR-mutated tumours as a genetic driver of disease, which occur in 15-20% of NSCLC patients globally and 30-40% of NSCLC patients in Asia, with our approved medicines Iressa and Tagrisso and on-going FLAURA and ADAURA trials. Our extensive late-stage immuno-oncology programme focuses on 75-80% of patients with NSCLC without a known genetic mutation. Our portfolio includes Imfinzi (durvalumab), an anti-PDL1 antibody, which is in development as monotherapy (ADJUVANT, PACIFIC, MYSTIC, PEARL and ARCTIC trials) and in combination with tremelimumab, anti-CTLA-4 (MYSTIC, NEPTUNE and POSEIDON trials).

On May 11, 2017 RXi Pharmaceuticals Corporation (NASDAQ: RXII), a clinical-stage RNAi company developing innovative therapeutics that address significant unmet medical needs, today reported its financial results for the first quarter ended March 31, 2017, and provided a business update (Press release, RXi Pharmaceuticals, MAY 11, 2017, View Source [SID1234519063]).

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"During the first quarter of 2017, RXi has been integrating MirImmune into its existing R&D operations. Through careful planning and execution of this integration, the Company has been able to maintain its cash use in line with that of last year," said Dr. Geert Cauwenbergh, President and CEO of RXi Pharmaceuticals. He also commented that, "RXi has added two new executives to its senior management team who will be instrumental in driving the development of novel therapeutics. Dr. Gerrit Dispersyn as Chief Development Officer and Dr. Alexey Eliseev as Chief Business Officer will provide significant leadership in the new and exciting space of immuno-oncology and cell therapy, while we continue to advance our dermatology and ophthalmology trials toward our planned readouts later this year." He further added that, "Recently, RXi also announced that Dr. Pamela Pavco will retire this month. During her tenure as Chief Development Officer, she has been an integral part of the development of RXi’s technology platform and clinical programs. We are grateful that she will remain involved with the Company as part of its Scientific Advisory Board where her expertise in the field of oligonucleotides will continue to support the advancement of our development pipeline."

The Company will host a conference call today at 4:30 p.m. EDT to discuss financial results and provide an update on the Company. The webcast link will be available under the "Investors – Event Calendar" section of the Company’s website, www.rxipharma.com. The event may also be accessed by dialing toll-free in the United States +1 844-376-4678. International participants may access the event by dialing: +1 209-905-5958. An archive of the webcast will be available on the Company’s website approximately two hours after the presentation.

Select First Quarter 2017 Financial Highlights
Cash Position
At March 31, 2017, the Company had cash of $10.2 million, compared with $12.9 million at December 31, 2016. The Company believes that its existing cash should be sufficient to fund operations for at least the next twelve months.
Research and Development Expenses
Research and development expenses for the quarter ended March 31, 2017 were $1.3 million, which included less than $0.1 million of non-cash stock-based compensation expense, as compared with $1.3 million for the quarter ended March 31, 2016, which included $0.1 million of non-cash stock-based compensation expense.

Research and development expenses were consistent quarter over quarter, but did see slight increases due to the commencement of the Company’s new immunotherapy program with the acquisition of MirImmune Inc.

("MirImmune"), a privately-held biotechnology company that was engaged in the development of cancer immunotherapies, in January 2017, which were offset by a decrease in stock-based compensation expense.

Acquired In-process Research and Development
The Company had acquired in-process research and development expense of $3.0 million for the quarter ended March 31, 2017. There was no such expense for the three months ended March 31, 2016. The expense related to the Company’s acquisition of MirImmune in January 2017. Per the terms of the acquisition, the Company acquired all of the issued and outstanding capital stock of MirImmune in exchange for shares of the Company’s common stock and Series C Convertible Preferred Stock, which were subject to a 3% holdback for any purchase price adjustments. The fair value of the consideration given during the quarter totaling $3.0 million was expensed as in-process research and development expense. The fair value of the securities subject to the 3% holdback, which were released and issued on April 12, 2017, will be recorded as in-process research and development expense during the second quarter of 2017.

General and Administrative Expenses
General and administrative expenses for the quarter ended March 31, 2017 were $1.1 million, which included $0.1 million of non-cash stock-based compensation expense, as compared with $1.0 million for the quarter ended March 31, 2016, which included $0.2 million of non-cash stock-based compensation expense.
The increase in general and administrative expenses was due to an increase in employee headcount with the hire of the Company’s Chief Business Officer as part of the acquisition of MirImmune and an increase in legal fees, offset by a decrease in stock-based compensation expense.
Net Loss
Net loss for the three months ended March 31, 2017 was $5.5 million, compared with $2.2 million for the three months ended March 31, 2016. The increase in net loss was primarily driven by the one-time charge of $3.0 million of acquired in-process research and development expense related to the acquisition of MirImmune in January 2017.
Select First Quarter 2017 and Recent Corporate Highlights
Select Business and Corporate Highlights
Management Team: The Company announced that Dr. Pamela Pavco, RXi’s Chief Development Officer, will retire effective May 19, 2017. At that time, Dr. Pavco will join the Company’s Scientific Advisory Board where her expertise in the field of oligonucleotides and the development of RNAi therapeutics will continue to support RXi’s ongoing research and development initiatives.
On April 24, 2017, Dr. Gerrit Dispersyn was appointed as RXi’s new Chief Development Officer. Dr. Dispersyn brings a wealth of experience to RXi as an accomplished leader in clinical, product and business development.
Intellectual Property Estate: The Company has been diligent and proactive with its approach to broadly protect its valuable corporate assets by securing patent protection for its RNAi platform and Samcyprone, a small molecule that is a proprietary ointment formulation of diphenylcyclopropenone (DPCP).
Most recently, the Company was granted a patent by the Japan Patent Office (JPO) for the composition of matter of sd-rxRNAs targeting connective tissue growth factor (CTGF) for the treatment or prevention of fibrotic disorders, including but not limited to skin fibrosis and proliferative vitreoretinopathy. This patent includes the Company’s lead clinical candidate RXI-109, an sd-rxRNA therapeutic compound, which is currently being evaluated in Phase 2 clinical trials.
Our portfolio currently includes 79 issued patents and 60 pending applications. This includes coverage in the United States, Canada, Europe, Japan and other markets. In addition, Samcyprone has been granted orphan-drug designation for malignant melanoma stage IIb to IV. The Company’s intellectual property estate provides for numerous commercial, regional and strategic partnering opportunities.
Development Programs
Immuno-oncology: The Company’s ongoing program to develop cell-based immunotherapies to treat cancer is based on our proprietary self-delivering RNAi (sd-rxRNA) technology platform. RXi’s novel sd-rxRNA technology differs from natural and most synthetic RNA interference (RNAi) molecules in that they are chemically modified to allow for an easy internalization of the compounds by most types of cells and silencing of the targeted genes.
sd-rxRNA offers unprecedented flexibility in targeting immunosuppressive pathways with the potential to modulate multiple checkpoint genes in a single therapeutic treatment. The built-in delivery and therapeutic properties of sd-rxRNA lend themselves well for local therapeutic applications, such as ex vivo treatment of the immune cells. The ex vivo use of sd-rxRNA to pre-treat immune cells prior to infusion may prove advantageous as an immuno-therapeutic in that there is the potential to simultaneously reduce multiple checkpoints or targets, including both intracellular and extracellular targets, with little change to current protocols. As outlined at the beginning of the year in our 2017 Corporate Goals, we are actively working on multiple checkpoint-inhibiting sd-rxRNA compounds co-transfected in CAR T-cells in mouse models for solid tumors and conducting preclinical studies on the use of sd-rxRNA with tumor infiltrating lymphocytes (TILs) in melanoma. Data from this ongoing work is expected to be available in the second half of 2017.
RXI-109-1402 – Hypertrophic Scarring: The Company’s ongoing Phase 2 clinical trial, RXI-109-1402, is being conducted to evaluate its first clinical candidate RXI-109, an sd-rxRNA compound targeting connective tissue growth factor (CTGF) to reduce scar formation in the skin following scar revision surgery. The Company will provide a full read-out, for Cohorts 3 and 4, in the second half of 2017.
RXI-109-1501 – Retinal Scarring in Advanced Age-related Macular Degeneration (AMD): As in dermal scarring, CTGF is known to play a role in retinal scarring. Reduction of CTGF in the eye by RXI-109 treatment may reduce the formation of retinal fibrosis that often accompanies late stage AMD and contributes to permanent vision loss. Enrollment in the first two cohorts in the Company’s Phase 1/2 trial, RXI-109-1501, is complete. RXI-109 has been well-tolerated in the eye to date; enrollment into the third cohort at the next higher dose level is ongoing.
RXI-SCP-1502 – Treatment of Cutaneous Warts: Samcyprone, the Company’s second clinical candidate, is being evaluated in a Phase 2a clinical trial. RXI-SCP-1502 is a multi-center, multi-dose trial conducted in subjects with at least one cutaneous, plantar or periungual wart. The Company expects to share early read-outs in the second half of 2017.
Consumer/Functional Health Care: The Company presented an update on its consumer health program at the 76th annual meeting of the Society for Investigative Dermatology. RXI-231, an sd-rxRNA targeting tyrosinase, is in development as a cosmetic ingredient that may improve the appearance of uneven skin tone and pigmentation. RXi has developed a proprietary formulation that allows for the non-invasive penetration of sd-rxRNA compounds to the epidermal-dermal junction where the reduction of tyrosinase in the resident melanocytes would lead to a reduction of melanin. We are in the process of finalizing the first two protocols for testing in volunteers.
RXI-185, an sd-rxRNA targeting MMP1, is in development as a cosmetic ingredient that may improve the appearance of wrinkles, skin laxity or photo-aging. A study conducted in collaboration with DSM, showed that RXI-185 is capable of reducing MMP1 mRNA levels following topical administration in an ex vivo human skin model. A topical formulation of RXI-185 is currently in development to lessen the effects of photo-aging.