On July 6, 2016 Evotec AG (Frankfurt Stock Exchange: EVT, TecDAX, ISIN: DE0005664809) reported that the Company has entered into a non-exclusive licence agreement with the Broad Institute of MIT and Harvard for the use of CRISPR-Cas9 gene editing technology (Press release, Evotec, JUL 6, 2016, View Source [SID:1234513728]).

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Under the terms of this research tool licence, Evotec gains access to IP related to CRISPR-Cas9 and will apply the technology to its drug discovery offerings and R&D activities, especially for the development of research tools and in target identification, and to further strengthen its post phenotypical screening target deconvolution platform.

With this agreement, Evotec obtains non-exclusive access to the leading technology on the market for gene editing.

Dr Mario Polywka, Chief Operating Officer of Evotec, commented: "Alongside Evotec’s comprehensive stem cell capabilities, the ability to offer CRISPR-Cas9 research tools emphasises the Company’s continuing approach to establishing cutting-edge technologies for the benefit of our partners and growing R&D pipeline."

ABOUT THE CRISPR-CAS9 SYSTEM
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a naturally-occurring bacterial immune system. Researchers have harnessed this system as a genome editing tool for mammalian cells. The CRISPR-Cas9 gene editing system allows researchers to target specific genes, to mutate these and achieve knock out or enhance the expression of these in living cells. Through application of the CRISPR-Cas9 technology, valuable insights into the functions of these genes in disease establishment and progression can be gained.

On July 6, 2016 Merrimack Pharmaceuticals, Inc. (Nasdaq: MACK) reported that the U.S. Food and Drug Administration (FDA) has granted seribantumab, also known as MM-121, Fast Track designation for development in patients with heregulin-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has progressed following immunotherapy (Press release, Merrimack, JUL 6, 2016, View Source [SID:1234513745]). Fast Track is a program designed by the FDA to facilitate and expedite the development and review of drugs that treat serious conditions and fill an unmet medical need. Merrimack is conducting the SHERLOC trial, a global clinical study of seribantumab in combination with docetaxel or pemetrexed in heregulin-positive patients with NSCLC that is designed to support a Biologics License Application to the FDA. Seribantumab is Merrimack’s wholly owned, fully human monoclonal antibody that targets ErbB3.

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"We are pleased that the FDA recognizes the importance of investigating a novel, biomarker-directed agent such as seribantumab for patients with locally advanced or metastatic NSCLC who have been previously treated with an immunotherapy," said Dr. Akos Czibere, Vice President, Clinical Development at Merrimack. "Heregulin-positive cancer cells are characterized by their ability to escape the effects of a broad range of cancer therapies and potentially contribute to accelerated disease progression. The SHERLOC trial is designed to advance the development of a much-needed treatment option for patients with heregulin-positive NSCLC after they progress on immunotherapies. This is important because we find that more than 50% of patients with NSCLC are heregulin-positive."

Heregulin-positive disease has been linked to rapid progression and poor prognosis in multiple types of cancer, including NSCLC. The higher the prevalence of heregulin-positive cancer cells in a tumor, the lower the anti-tumor effect of the chemotherapy. Seribantumab is designed to block heregulin-driven signaling and enhance the anti-tumor effect of the chemotherapy. Data from Merrimack’s prior clinical studies have shown that standard-of-care therapy may be more effective and result in improved patient outcomes when combined with seribantumab. Merrimack is investigating the efficacy and safety of seribantumab plus standard-of-care therapy in the SHERLOC trial.

Lung cancer is the leading cause of cancer-related death in the United States. The American Cancer Society estimates that approximately 224,000 new cases of lung cancer (both small cell lung cancer and NSCLC) will be reported in 2016, 83% of which will be NSCLCi. Merrimack estimates that approximately 101,000 U.S. NSCLC patients will have heregulin-positive tumors, based on the prevalence seen in data presented by Merrimack at the 2014 European Society for Medical Oncology Congressii.

About the SHERLOC Trial

The SHERLOC trial is a randomized, open-label, multi-center, Phase 2 study in patients with heregulin-positive, locally advanced or metastatic NSCLC. Merrimack expects to enroll approximately 280 heregulin-positive patients who will be randomized (2:1) to receive seribantumab in combination with either docetaxel or pemetrexed versus docetaxel or pemetrexed alone. Patients will be screened for heregulin status using a fully validated RNA-ISH assay (in situ hybridization). Eligible patients for the study must have failed prior treatment with no more than three lines of therapy including prior anti-PD-1 or anti-PD-L1 immunotherapy. The study’s primary endpoint is overall survival with secondary endpoints including progression free survival, objective response rate, safety and quality of life measures. The study is designed to support a Biologics License Application to the FDA with data expected in 2018. For more information on this trial, please visit www.clinicaltrials.gov (Identifier: NCT02387216).

About Seribantumab (MM-121)

Seribantumab is Merrimack’s wholly owned, fully human anti-ErbB3 monoclonal antibody that targets phenotypically distinct heregulin-positive cancer cells within solid tumors. Heregulin-positive cancer cells are characterized by their ability to escape the effects of targeted, cytotoxic and anti-endocrine therapies and potentially contribute to rapid clinical progression in patients whose tumor cells test positive for heregulin as detected by RNA-ISH. When used in the combination setting, seribantumab is designed to block the heregulin/ErbB3 signaling axis in order to make these cells accessible to the effects of the combination therapy and potentially lead to significantly improved clinical outcomes.

Merrimack is also developing its novel heregulin assay for seribantumab into a kit for commercial use under a partnership agreement with Leica Biosystems.

On July 6, 2016 Seattle Genetics, Inc. (NASDAQ:SGEN) reported that its collaborator Takeda Pharmaceutical Company, Limited, received marketing authorization by the European Commission for ADCETRIS (brentuximab vedotin) for the treatment of adult patients with CD30+ Hodgkin lymphoma at increased risk of relapse or progression following autologous stem cell transplant (ASCT) (Press release, Seattle Genetics, JUL 6, 2016, View Source [SID:1234513738]). The approval is based on a phase 3 clinical trial called AETHERA that was designed to compare up to 16 cycles (approximately one year) of ADCETRIS therapy administered every three weeks following ASCT to placebo. This label expansion represents the third indication for ADCETRIS in the European Union (EU), and follows U.S. Food & Drug Administration approval in August 2015 for a similar label based on the AETHERA clinical trial.

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"With the European Commission approval, ADCETRIS becomes the first and only consolidation treatment option available in both the United States and European Union for high risk classical Hodgkin lymphoma patients to preserve their remission post-transplant," said Clay Siegall, Ph.D, President and Chief Executive Officer of Seattle Genetics. "This continues to support our goal to establish ADCETRIS as the global foundation of therapy for classical Hodgkin lymphoma and CD30-expressing lymphomas and provides a meaningful advance for cancer patients."

The conditional marketing authorization for ADCETRIS is valid in the 28 member states of the EU as well as Norway, Liechtenstein and Iceland.

About ADCETRIS

ADCETRIS is being evaluated broadly in more than 70 ongoing clinical trials, including the phase 3 ALCANZA trial, ECHELON-1 in frontline classical HL and ECHELON-2 in frontline mature T-cell lymphomas, as well as trials in several additional types of CD30-expressing lymphomas, including B-cell lymphomas.

ADCETRIS is an ADC comprised of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS for intravenous injection has received approval from the FDA for three indications: (1) regular approval for the treatment of patients with classical HL after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (2) regular approval for the treatment of classical HL patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Health Canada granted ADCETRIS approval with conditions for relapsed or refractory HL and sALCL.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). In January 2016, the European Commission approved a Type II variation to include data on the retreatment of adult patients with Hodgkin lymphoma or sALCL who previously responded to ADCETRIS and who later relapse. ADCETRIS has received marketing authorization by regulatory authorities in more than 60 countries.

In June 2016, the European Commission extended the current conditional approval of ADCETRIS and approved ADCETRIS for the treatment of adult patients with CD30+ Hodgkin lymphoma at increased risk of relapse or progression following autologous stem cell transplant (ASCT). See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

ADCETRIS (brentuximab vedotin) U.S. Important Safety Information

BOXED WARNING

Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.

Contraindication

ADCETRIS is contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

Warnings and Precautions

Peripheral neuropathy (PN): ADCETRIS treatment causes a PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness and institute dose modifications accordingly.
Anaphylaxis and infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion-related reaction occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Patients who experienced a prior infusion-related reaction should be premedicated for subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.
Hematologic toxicities: Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS. Febrile neutropenia has been reported with ADCETRIS. Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.
Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in patients treated with ADCETRIS. Closely monitor patients during treatment for the emergence of possible bacterial, fungal or viral infections.
Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.
Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment compared to patients with normal renal function. Avoid the use of ADCETRIS in patients with severe renal impairment.
Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment compared to patients with normal hepatic function. Avoid the use of ADCETRIS in patients with moderate or severe hepatic impairment.
Hepatotoxicity: Serious cases of hepatotoxicity, including fatal outcomes, have occurred with ADCETRIS. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first dose of ADCETRIS or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may also increase the risk. Monitor liver enzymes and bilirubin. Patients experiencing new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS therapy, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
Pulmonary toxicity
Events of noninfectious pulmonary toxicity including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, some with fatal outcomes, have been reported. Monitor patients for signs and symptoms of pulmonary toxicity, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.
Serious dermatologic reactions: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), including fatal outcomes, have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy.
Gastrointestinal (GI) complications: Fatal and serious GI complications, including perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus have been reported in ADCETRIS-treated patients. Lymphoma with preexisting GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, perform a prompt diagnostic evaluation and treat appropriately.
Embryo-fetal toxicity: Based on the mechanism of action and findings in animals, ADCETRIS can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should avoid pregnancy during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.
Adverse Reactions

In two uncontrolled single-arm trials of ADCETRIS as monotherapy in 160 patients with relapsed classical HL and sALCL, the most common adverse reactions (≥20%), regardless of causality, were: neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.

In a placebo-controlled trial of ADCETRIS in 329 patients with classical HL at high risk of relapse or progression post-auto-HSCT, the most common adverse reactions (≥20%) in the ADCETRIS-treatment arm (167 patients), regardless of causality, were: neutropenia, peripheral sensory neuropathy, thrombocytopenia, anemia, upper respiratory tract infection, fatigue, peripheral motor neuropathy, nausea, cough, and diarrhea.

Drug Interactions

Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to monomethyl auristatin E (MMAE).

Use in Specific Populations

MMAE exposure and adverse reactions are increased in patients with moderate or severe hepatic impairment or severe renal impairment. Avoid use.

Advise females of reproductive potential to avoid pregnancy during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.

Advise males with female sexual partners of reproductive potential to use effective contraception during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.

Advise patients to report pregnancy immediately and avoid breastfeeding while receiving ADCETRIS.

For additional Important Safety Information, including Boxed WARNING, please see the full Prescribing Information for ADCETRIS at www.seattlegenetics.com or www.ADCETRIS.com.

On July 06, 2016 Advaxis, Inc. (NASDAQ:ADXS), a clinical stage biotechnology company developing cancer immunotherapies, reported that it reached an agreement with the U.S. Food and Drug Administration (FDA), under the Special Protocol Assessment (SPA) process, for the Phase 3 AIM2CERV trial evaluating the Company’s lead Lm immunotherapy candidate, axalimogene filolisbac (AXAL), in patients with high-risk, locally advanced cervical cancer (HRLACC) (Press release, Advaxis, JUL 6, 2016, http://ir.advaxis.com/press-releases/detail/1226/fda-grants-special-protocol-assessment-to-advaxis-phase-3-study-of-axal-in-patients-with-cervical-cancer [SID:1234513736]). AIM2CERV is a multinational, randomized, controlled clinical trial conducted in collaboration with The GOG Foundation, Inc. Trial enrollment will commence this summer.

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A successfully concluded SPA provides a binding agreement with FDA’s review division that a pivotal trial design, conduct, and planned analysis adequately address the scientific and regulatory objectives in support of a regulatory submission for drug approval. Final marketing approval depends upon the efficacy results, safety profile and an evaluation of the risk/benefit of treatment demonstrated in the Phase 3 clinical trial.

In the 10-year period ending in 2013, only 25 percent of the requests for a SPA of oncology trials concluded with an FDA agreement.

"Receiving a SPA for the AIM2CERV trial is a testament to the promising AXAL results we have seen in cervical cancer patients," said Bradley Monk, M.D., Professor and Director of the Division of Gynecologic Oncology at Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center and Lead Cervical Cancer Advisor to Advaxis. "The AIM2CERV trial will be a critical step in demonstrating that AXAL can be successful as an immunotherapy, with the trial’s goal to cure more women, and prevent disease recurrence."

"Collaborative discussions with the FDA led to a positive outcome with a SPA that clearly defines the clinical and regulatory pathway for the approval and commercialization of AXAL for the treatment of patients with HRLACC," said Daniel J. O’Connor, President and Chief Executive Officer. "Obtaining a SPA for the AIM2CERV Phase 3 protocol was our number one priority this year and it has now been achieved."

AXAL is a live attenuated Listeria monocytogenes bacteria bioengineered to target HPV-associated cancer. The primary objective of AIM2CERV is to compare the disease free survival of AXAL to placebo administered in the adjuvant setting following concurrent chemotherapy and radiotherapy (CCRT) administered with curative intent to patients with HRLACC. Secondary endpoints include examining overall survival and safety.

About Special Protocol Assessment

A SPA is an agreement with the FDA that the proposed trial protocol design, clinical endpoints and statistical analyses are acceptable to support the submission of an application for FDA’s determination of regulatory approval. For further information regarding the SPA process, please visit the FDA website, www.fda.gov.

About Cervical Cancer

Cervical cancer is the third most common malignancy in women worldwide. In the United States, nearly 13,000 new cases are diagnosed, and approximately 4,100 deaths are reported due to cervical cancer. According to the WHO/ICO Information Centre on HPV and Cervical Cancer, about 3.9 percent of women in the United States are estimated to harbor high-risk cervical HPV infection at a given time, and 71.7 percent of invasive cervical cancers are attributed to high-risk HPV strains.

About Axalimogene Filolisbac

Axalimogene filolisbac (AXAL) is Advaxis’ lead Lm Technology immunotherapy candidate for the treatment of patients with HPV-associated cancers and is in clinical trials for three potential indications: invasive cervical cancer, head and neck cancer, and anal cancer. In a completed randomized Phase 2 study in recurrent/refractory cervical cancer, AXAL showed apparent prolonged survival, objective tumor responses, and a manageable safety profile alone or in combination with chemotherapy, supporting further development of the Company’s Lm Technology. AXAL has Orphan Drug Designation in the U.S. for the treatment of anal cancer.