On June 12 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported an update on two combination studies of KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, in the blood cancer multiple myeloma (Press release, Merck & Co, JUN 12, 2017, View Source [SID1234519544]). Merck has accepted the external Data Monitoring Committee recommendation to pause new enrollment on KEYNOTE-183 and KEYNOTE-185, two studies exploring KEYTRUDA treatment in combination with other therapies in multiple myeloma. The pause is to allow for additional information to be collected to better understand more reports of death in the KEYTRUDA groups. Patients currently enrolled in these two studies will continue to receive treatment. Other studies of KEYTRUDA continue unchanged.

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KEYNOTE-183 is a Phase 3 study comparing pomalidomide and low-dose dexamethasone with KEYTRUDA to pomalidomide and low-dose dexamethasone alone in patients with refractory or relapsed and refractory multiple myeloma (rrMM) who have undergone at least 2 lines of prior treatment. KEYNOTE-185 is a Phase 3 study comparing lenalidomide and low-dose dexamethasone with KEYTRUDA to lenalidomide and low-dose dexamethasone alone in patients with newly diagnosed and treatment-naïve multiple myeloma who are ineligible for autologous stem cell transplant (Auto-SCT).

KEYTRUDA (pembrolizumab) Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA (pembrolizumab), as a single agent, is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, as a single agent, is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

KEYTRUDA, in combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous NSCLC. This indication is approved under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

In metastatic NSCLC, KEYTRUDA (pembrolizumab) is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA should be administered prior to chemotherapy when given on the same day. See also the Prescribing Information for pemetrexed and carboplatin.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after three or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In adults with cHL, KEYTRUDA (pembrolizumab) is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with cHL, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

KEYTRUDA is also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

In locally advanced or metastatic urothelial carcinoma, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) cancer or mismatch repair deficient (dMMR):

solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

The safety and effectiveness of KEYTRUDA (pembrolizumab) in pediatric patients with MSI-H central nervous system cancers have not been established.

In adult patients with MSI-H cancer, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with MSI-H cancer, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA (pembrolizumab) for Grade 3 or 4 hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

KEYTRUDA can cause other clinically important immune-mediated adverse reactions. These immune-mediated reactions may occur in any organ system. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), exfoliative dermatitis, bullous pemphigoid, rash (1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.

Solid organ transplant rejection has been reported in postmarketing use of KEYTRUDA. Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment with KEYTRUDA vs the risk of possible organ rejection in these patients.

KEYTRUDA (pembrolizumab) can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and symptoms of infusion-related reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC. The most common adverse event resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to interruption of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common adverse reactions (occurring in at least 20% of patients and at a higher incidence than with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea (20% vs 18%).

It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program that includes more than 500 clinical trials evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic candidates with the potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

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On December 12, 2017 Selexis SA and TeneoBio, Inc. reported that they have entered into a service agreement to advance the development of a new class of biologics, Human Heavy-Chain Antibodies (UniAbs) targeting cancer (Press release, Selexis , DEC 12, 2017, View Source [SID1234533030]). Under the agreement, TeneoBio will leverage Selexis’ proprietary SUREtechnology Platform to develop and optimize the cellular expression of multi-specific UniAbs that were discovered using TeneoBio’s proprietary sequence-based TeneoSeek discovery engine and UniRat Human Heavy-Chain Antibody Platform.

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"TeneoBio is developing a new class of multispecific biologics for treatments of multiple myeloma, lymphoma and prostate cancer," said Yemi Onakunle, PhD, vice president, business development and licensing with Selexis. "We believe in the power of the Selexis SUREtechnology Platform to help TeneoBio to rapidly and predictably achieve the high antibody expression levels and cell line stability that are needed for the cost-effective production of their unique multi-specific antibody candidates."

Selexis’ SUREtechnology platform facilitates the rapid, stable, and cost-effective production of virtually any recombinant protein, including those that are difficult to express in other systems. It also provides seamless integration of the biologics and vaccine development continuum, spanning discovery to commercialization.

Omid Vafa, chief business officer at TeneoBio, Inc., added, "This is the first of several TeneoBio bi- and multi-specific UniAb candidates that leverages our unique T-cell redirection platform to target liquid and solid tumors. We are excited to work with Selexis, a pioneer in bioproduction that offers the right balance of speed, technology, and flexibility to generate cell lines for our lead program."

Belén Garijo CEO Healthcare Luciano Rossetti Global Head of Research & Development, Biopharma Rehan Verjee Chief Marketing and Strategy Officer, Healthcare June 12, 2017 Biopharma R&D pipeline Update Complete portfolio supporting leadership in a potentially disruptive class DNA damage response (DDR) Genomic instability: a hallmark of late stage cancers 1 • DNA damage response (DDR) keeps genetic information intact • In many cancers DDR pathways are defected, leading to greater dependency on remaining functional DDR pathways • Preferentially inhibiting remaining DDR pathways can result in cancer cell death ("synthetic lethality") 26 1 Sources : O’Connor, Molecular Cell, 2015 | Benjamin et al., Current Drug Targets, 2010, 11, 1336-1340 2 "A multicenter phase I trial of the DNA-dependent protein kinase (DNA-PK) inhibitor M3814 in patients with solid tumors", Mark van Bussel, ASCO (Free ASCO Whitepaper) 2017 Acronyms: ATM: ataxia-telangiectasia mutated |ATR: ataxia telangiectasia and Rad3 | DNA-PK: DNA-dependent protein kinase | Amplifying cytotoxic effects of conventional and novel cancer treatments potentially bears combination potential 1. Inhibitor portfolio targets all three leading pathways of double stranded breaks – enabling unique synergies 2. ASCO (Free ASCO Whitepaper) 2017: leading DNA-PK-I (M3814) found safe and tolerable in a phase I study, with limited single-agent activity (20 % of patients with stable disease for at least 18 weeks) 2 3 Lead Optimization Pre-clinical Phase I Phase II Phase III 28 DNA-PK-i ATR-i ATM-i VX-970 VX-803 VX-984 M-3814 M-3541 Clinical program targets all three DDR pathways, in mono-and combination Acronyms: ATM: ataxia-telangiectasia mutated |ATR : ataxia telangiectasia and Rad3 | DNA-PK: DNA-dependent protein kinase | CT : Chemotherapy | RT: Radiotherapy | Note : timelines are event-driven and may change Phase IB expansion cohorts ongoing in combination with CT (TNBC, NSCLC, SCLC) Phase I dose escalation ongoing for mono-and combination therapy (with CT) Phase I dose escalation ongoing in combination with CT (licensed-in) Two Phase Ib /II proof-of-concept studies in combination with CT and RT ongoing Expected to enter clinic in 2017 DNA damage response (DDR) 3 29 DNA damage response (DDR) Broad combination potential across multiple mechanisms Combination with CT ATR DNA-PK ATM Combination with DDR Combination with ADC Combination with IO Monotherapy Combination with RT At least 50% of all cancer patients receive some type of RADIATION therapy (NCI 2016) At least 70% of all cancer patients receive some type of CHEMOTHERAPY (NCI 2016) Significant share of patients to be treated with CHECKPOINT INHIBITORS 4 3 30 Early stage strengthened – enabling late stage optionality across all TAs 1 Pipeline Immuno-Oncology Immunology Phase I Phase II Phase III Oncology New in pipeline Moved to next phase Maintained position BTK inhibitor RA sprifermin Osteoarthritis Avelumab RCC 1L 1 Tepotinib HCC Avelumab NSCLC 2L 2 Avelumab Gastric 1L MN 1 Avelumab Urothelial 1L MN 1 Avelumab Ovarian plat. res./ref Avelumab Ovarian 1L (Chemo) 1 BTK inhibitor SLE tepotinib NSCLC Avelumab Gastric 3L 3 Avelumab LA SCCHN Atacicept SLE Avelumab NSCLC 1L 1 Biosimilars Adalimumab biosimilar Chr. plaque Psoriasis R Registered (US) Abituzumab SSc-ILD Externalized p70S6K & Akt-i Solid tumors DNA-PK-i Solid tumors BRAF-I (Beigene) Solid tumors BTK inhibitor Hem. malignancies Avelumab Solid tumors Avelumab Hem. malignancies anti-PD-L1/TGF-b trap Solid tumors Avelumab MCC 1L Anti-IL-17 A/F Psoriasis Avelumab 5 Merkel cell (EU) R BTK inhibitor MS DNA-PK-I (VX-984) Solid tumors ATR-i 7 (VX-970) Solid tumors ATR-I (VX-803) Solid tumors Filing Cladribine Tablets RMS (EU) ATX-MS-1467 MS Avelumab + NHS IL 12 Solid tumors Avelumab+41BB/OX40 Solid tumors Avelumab comb.** DLBCL Terminated 2 Atacicept IgA Nephropathy Avelumab (mono/combo) Various ISTs 1 Since R&D Update call on June 20, 2016 | 2 Either terminated (ATX, BRAF-i) or divested (Biosimilars) | Acronyms: SLE = systemic lupus erythematosus, RRMS = relapse remitting multiple sclerosis, NSCLC = non-small cell lung cancer, HCC = hepatocellular carcinoma, STS = soft-tissue carcinoma, MCC = Merkel cell ca rcinoma, RA = rheumatoid arthritis, SCCHN = squamous cell cancer of the head and neck, SSC-ILD: Systemic sclerosis with interstitial lung disease | DLBCL: Diffuse Large B-cell Lymphoma

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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