On June 8, 2017 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported that it has commenced its phase 3 clinical program to evaluate the efficacy of Inovio’s DNA-based immunotherapy, VGX-3100, to treat cervical dysplasia caused by human papillomavirus (HPV) (Press release, Inovio, JUN 8, 2017, View Source [SID1234519479]). Inovio’s study will assess the efficacy of VGX-3100 in regressing cervical HSIL (high-grade squamous intraepithelial lesions), a direct precursor to cervical cancer, and eliminating the HPV infection that causes these lesions. The pivotal data from this program will support the potential licensure of VGX-3100 as the first immunotherapy for this disease.

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Inovio satisfied the FDA’s request for information relating to its CELLECTRA 5PSP delivery device, resulting in the FDA removing the clinical hold on this program. Inovio plans to immediately begin recruiting patients for the phase 3 trial.

Inovio’s phase 3 program, named REVEAL (Randomized Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL), will consist of a primary study (REVEAL 1) and confirmatory study (REVEAL 2), as per FDA general guidance for phase 3 programs, to be conducted in parallel. The studies will each enroll 198 patients in more than 100 study centers globally. Mark Einstein, MD, MS, FACS, FACOG, Professor and Chair Department of Obstetrics, Gynecology and Women’s Health Assistant Dean, Clinical Research Unit, Rutgers New Jersey Medical School, is Principal Investigator for the studies.

The REVEAL studies are prospective, randomized (2:1), double-blind, placebo-controlled trials evaluating adult women with HPV 16/18 positive biopsy-proven cervical HSIL, otherwise known as cervical intraepithelial neoplasia (CIN) 2 or 3. The primary endpoint is regression of cervical HSIL AND virologic clearance of HPV-16 and/or HPV-18 in the cervix. The studies will evaluate cervical tissue changes at approximately 9 months after beginning a three dose regimen of VGX-3100 administered at months 0, 1, and 3. Secondary endpoints include safety; tolerability; regression of CIN 2/3 to CIN 1 or normal; virologic clearance of HPV; efficacy measured by non-progression to cancer; and clearance of HPV from non-cervical anatomic locations.

VGX-3100 has the potential to be the first treatment for HPV infection of the cervix and the first non-surgical treatment for pre-cancerous cervical lesions. VGX-3100 stimulates a specific immune response to HPV-16 and HPV-18, targeting the infection and destroying pre-cancerous cells. There are no treatments available for HPV infection and surgery is the only approved treatment for cervical HSIL. While surgery is effective at removing dysplastic lesions, it does not treat the underlying HPV infection and carries increased risk of cervical incompetence and pre-term birth, which can result in fetal morbidity and mortality. VGX-3100 demonstrated in a phase 2b study (published in The Lancet) its ability to clear HPV-16 and HPV-18 infection and pre-cancerous lesions.

Dr. Mark Bagarazzi, Inovio’s Chief Medical Officer, said, "Despite the availability of preventive HPV vaccines for over a decade, HPV-related cervical HSIL and cancers remain a widely prevalent problem. Unfortunately, current treatments are invasive and do not address the underlying HPV infection. VGX-3100 has the potential to be a first-in-class HPV-specific immunotherapy offering women the prospect of preventing cervical cancer without undergoing an invasive surgical procedure that may compromise their reproductive health. We are pleased to be able to immediately begin recruiting patients at the first 15 sites by the end of this month."

Dr. J. Joseph Kim, Inovio’s President and CEO, said, "Initiating our REVEAL phase 3 program marks a milestone for Inovio, for the next generation of DNA-based immunotherapies, and for women’s health. Combining this first phase 3 program with our previously announced phase 2 clinical trial of VGX-3100 for HPV-related vulvar neoplasia and our checkpoint inhibitor-based combination study with MedImmune/AstraZeneca targeting HPV associated cancers, Inovio is well positioned to comprehensively treat HPV-associated diseases across the continuum of HPV infection through to cancer in both men and women. Adding our recently announced collaborative immuno-oncology combination studies with Regeneron and Genentech, 2017 is a transformative year that is laying the foundation for multiple opportunities for important efficacy data."

About HPV and Cervical HSIL

HPV is the most common sexually transmitted infection, with over 14 million new infections annually. While many of these are transient infections, persistent high-risk infections can cause the formation of pre-cancerous lesions. Left untreated, women diagnosed with cervical HSIL are at increased risk of developing cervical cancer. HPV types 16 and 18 are responsible for 70% of cervical cancers, with more than 400,000 new cases of HPV 16/18 cervical HSIL annually in the US and Europe. Cervical cancer is a major global health problem, causing 260,000 deaths annually. While cervical HSIL and cervical cancer are the most well-known HPV related diseases, HPV is also a major cause of HSIL and cancer in the entire anogenital region and oropharynx. Currently there are no treatments available for HPV infection and surgery is the only approved treatment for cervical HSIL. While surgery is effective at removing lesions, it does not treat the underlying HPV infection and it carries increased risk of cervical incompetence and pre-term birth, which can result in fetal morbidity and mortality.

About VGX-3100

VGX-3100 is a DNA-based immunotherapy under investigation for the treatment of HPV-16 and HPV-18 infection and pre-cancerous lesions of the cervix (phase 3) and vulva (phase 2). VGX-3100 has the potential to be the first approved treatment for HPV infection of the cervix and the first non-surgical treatment for pre-cancerous cervical lesions. VGX-3100 works by stimulating a specific immune response to HPV-16 and HPV-18, which targets the infection and causes destruction of pre-cancerous cells. In a randomized, double-blind, placebo-controlled phase 2b study in 167 adult women with histologically documented HPV 16/18 cervical HSIL (CIN2/3), treatment with VGX-3100 resulted in a statistically significantly greater decrease in cervical HSIL and clearance of HPV infection vs. placebo. The most common side effect was injection site pain, and no serious adverse events were reported. VGX-3100 utilizes the patient’s own immune system to clear HPV-16 and HPV-18 infection and pre-cancerous lesions without the increased risks associated with surgery, such as loss of reproductive health and negative psychosocial impacts.

On June 8, 2017 2X Oncology, Inc. ("2X" or the "Company"), a precision medicine company developing targeted therapeutics to address significant unmet needs in women’s cancer, reported that it has obtained the Investigational New Drug (IND) application for 2X-111 (doxorubicin hydrochloride and glutathione) from 2-BBB Medicines B.V., assuming all future development and ownership of the drug (Press release, 2X Oncology, JUN 8, 2017, View Source [SID1234526104]).

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2X-111 is being developed as a new treatment option for women with brain metastases from breast cancer and for patients with recurrent glioblastoma multiforme (GBM), an orphan-designated condition.

George O. Elston, CEO of 2X Oncology, said, "Having this IND in place is an important step as we focus on initiating Phase 2 clinical trials of 2X-111 in GBM and brain metastases from breast cancer later this year.

"These studies will employ our proprietary DRP companion diagnostic to identify patients based on their unique tumor mRNA expression and treat those most likely to respond to and benefit from therapy," Mr. Elston added.

"Patient selection based on the unique genetic properties of a tumor is an important new direction in the treatment of cancer, and we are pleased to have this capability for our programs and patients."

The Drug Response Predictor (DRP) technology utilizes messenger RNA (mRNA) from patient biopsies and uses proprietary analytics to create a unique fingerprint of relevant genes based on a tumor’s sensitivity, or resistance, to a compound. DRPs are specific for each product and have been validated in over 40 clinical studies.

"We expect data from these studies in 2018 which, if positive, can position this program for possible accelerated approval filings shortly thereafter," Mr. Elston concluded.

Formerly known as 2B3-101, 2X-111 improves on commercially available PEGylated liposomal doxorubicin products with an additional glutathione coating that safely enhances drug delivery across the blood-brain barrier. Doxorubicin is an anthracycline that inhibits the growth of many cancerous cell lines, including glioblastoma and breast cancer cell lines. It is among the most widely used anti-cancer agents.

An abstract on the predictive ability of the DRP in treating advanced breast cancer with a similar anthracycline, epirubicin, was presented in a poster session at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

The abstract describes a retrospective-prospective blinded study which evaluated the ability of the DRP to predict the efficacy of epirubicin in a cohort of 135 metastatic breast cancer patients. The DRP was significantly associated with progression free survival in this study. The estimated median time to progression for a patient with a DRP value of 25% was 7 months, versus 13 months for a patient with a DRP value of 75%.

Mr. Elston will discuss 2X-111 and other 2X pipeline drugs at the Jefferies 2017 Global Healthcare Conference on June 9, 2017, at 10:00am EDT. The presentation will be available as a live webcast and archived for post-listening on the Company’s website.

About Breast Cancer Brain Metastases

Breast cancer is the second most common common cause of brain metastases, with metastases occurring in 10–16 % of patients[1]. Patients who develop brain metastases tend to have poor prognosis with short overall survival. Furthermore, brain metastases are a major cause of morbidity, associated with progressive neurologic deficits that result in a reduced quality of life.

About Glioblastoma Multiforme
Glioblastoma multiforme (GBM) is the most common class of malignant primary brain tumors and one of the most aggressive forms of cancer. This highly invasive and proliferative cancer resists standard chemotherapy and radiotherapy. Current therapeutic strategies for the treatment of GBM fail to demonstrate adequate efficacy and/or are generally palliative. Median overall survival is 12 to 14 months

On June 7, 2017 Midatech Pharma (AIM: MTPH; Nasdaq: MTP), the international specialty pharmaceutical company focused on commercialising and developing products in oncology, reported that it has signed a global licensing agreement with Novartis for the oncology compound panobinostat. Panobinostat will be developed by Midatech for the treatment of Diffuse Intrinsic Pontine Glioma (DIPG) as a continuation of its existing MTX110 program, and potentially for Glioblastoma (GBM) (Press release, Midatech Pharma, JUN 7, 2017, View Source [SID1234519676]).

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In pre-clinical test models, panobinostat, which is a pan-HDAC inhibitor, demonstrated very high potency against DIPG tumour cell lines. In one such study panobinostat was the most effective of more than 80 anti-cancer agents tested.

Midatech’s MTX110 program is focused on the treatment of DIPG, a childhood brain cancer that is nearly always fatal, with a median survival of approximately 9 months. Using a technique called Convection Enhanced Delivery, MTX110 is infused directly into the brain tumour, and diffuses through and around it. This technique allows for elevated drug concentrations to be delivered to the tumour, while at the same time minimizing systemic toxicity and peripheral side-effects. MTX110 has been used to treat 5 patients to date in the USA and UK under its compassionate use program. In these patients MTX110 has been well tolerated thus far. We believe it holds promise as a potential therapeutic treatment for DIPG, for which there are currently no approved or effective therapies. Clinical studies in patients are planned to commence during 2017. Financial terms have not been disclosed.

Jim Phillips, CEO of Midatech Pharma, said: "In line with our strategy to focus on oncology and expand our product mix, we are pleased that Novartis recognises our unique capability to use their product panobinostat alongside our technology to treat orphan cancers. We look forward to driving it through development for treatment of DIPG, and make a real difference to the children suffering from this devastating and terminal disease."

On June 5, 2017 Novartis reported it has entered into a clinical research collaboration in which Bristol-Myers Squibb will investigate the safety, tolerability, and efficacy of Mekinist (trametinib) in combination with Opdivo (nivolumab) and Opdivo + Yervoy (ipilimumab) regimen as a potential treatment option for metastatic colorectal cancer in patients with microsatellite stable tumors where the tumors are proficient in mismatch repair (MSS mCRC pMMR) (Press release, Novartis, JUN 5, 2017, View Source [SID1234519452]).

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Under the terms of the agreement, the study will be conducted by Bristol Myers-Squibb and is expected to establish recommended dose regimens and the preliminary anti-tumor activity of the combination therapies. Both Bristol Myers-Squibb and Novartis will evaluate the results to determine optimal approaches and potential clinical development of these combinations.

"Novartis has a longstanding heritage in exploring the combination of medicines to broaden our knowledge of mutational driven cancers and develop innovative treatments," said Vas Narasimhan, MD, Head, Global Drug Development and Chief Medical Officer, Novartis. "Along with our ongoing internal immuno-oncology efforts, the expansion of our collaboration with Bristol-Myers Squibb further advances our collective goals to advance the science and to support patients in need."

About Colorectal Cancer
Worldwide, colorectal cancer is the third most common type of cancer in men and the second most common in women, with approximately 1.4 million new diagnoses in 2012. Of these, nearly 750,000 were diagnosed in men, and 614,000 in women[1]. Globally in 2012, approximately 694,000 deaths were attributed to colorectal cancer[1]. In the U.S. alone, an estimated 135,430 patients will be diagnosed with cancer of the colon or rectum in 2017, and approximately 50,000 are estimated to die of their disease[2]. There is wide variation in 5-year survival rates across disease stages, with 5-year survival rates for patients with metastatic or stage IV colorectal cancer around 11%[3]. The incidence of microsatellite stability (MSS) in colorectal tumors varies by stage, with 80% to 85% of exhibiting MSS[4].

About Mekinist and Important Safety Information
MEKINIST is a kinase inhibitor indicated, as a single agent or in combination with dabrafenib, for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test. MEKINIST is not indicated for treatment of patients who have received prior BRAF-inhibitor therapy. MEKINIST can cause serious side effects including new primary malignancies (cutaneous and non-cutaneous), hemorrhage, inflammation of the colon and perforation of the intestines, blood clots in the legs, cardiomyopathy, eye toxicity, interstitial lung disease, serious fevers, serious skin toxicity, hyperglycemia, and harm to a fetus. Some of these side effects can be fatal in rare cases. The most common side effects when MEKINIST is used as a single-agent are rash, diarrhea, and lymphedema.

About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, Bristol-Myers Squibb’s Opdivo and Yervoy (link is external) combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

About Yervoy
Yervoy, which is a recombinant, human monoclonal antibody, blocks the cytotoxic T- lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activation. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation. The mechanism of action of Yervoy effect in patients with melanoma is indirect, possibly through T-cell mediated anti-tumor immune responses. On March 25, 2011, the FDA approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is now approved in more than 40 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types. This includes Phase 3 trials in prostate and lung cancers.

On June 5, 2017 Cornerstone Pharmaceuticals, Inc., a clinical-stage, oncology-focused pharmaceutical company, reported that it is changing its corporate name to Rafael Pharmaceuticals, Inc., effective immediately (Press release, Rafael Pharmaceuticals, JUN 5, 2017, View Source [SID1234521069]). The name change signifies a new era in the company’s evolution during which the company aims to usher in a new paradigm in anticancer treatment with its breakthrough metabolic cancer drugs. The new name is derived from Raphael, the biblical angel of healing.

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"Over the past few months we’ve gained a lot of momentum across several facets and this is an ideal moment to effectuate our name change," said Howard Jonas, Executive Chairman of Rafael Pharmaceuticals. "We’ve strengthened our company’s foundation by making key hires, by adding renowned scientists and clinicians to our advisory boards, and by adding leaders in the pharmaceutical and scientific research communities to our Board of Directors. Moreover, we’ve made substantial progress towards commercializing our proprietary Altered Energy Metabolism Directed (AEMD) drug platform. Most notably, we recently completed successful End-of-Phase I Type B Meetings with the FDA, and now have approval from the FDA to initiate pivotal trials for CPI-613 in acute myeloid leukemia (AML) and pancreatic cancer."