On June 19, 2016 Epizyme, Inc. (NASDAQ: EPZM), a clinical-stage biopharmaceutical company creating novel epigenetic therapies, reported preliminary data from its ongoing, global Phase 2 clinical trial of orally administered tazemetostat, a first-in-class EZH2 inhibitor, in relapsed or refractory patients with non-Hodgkin lymphoma (NHL) (Press release, Epizyme, JUN 19, 2016, View Source [SID:1234513457]). Early data from the Phase 2 trial indicate that tazemetostat demonstrated a favorable safety profile and clinical activity consisting of objective responses in a heavily pre-treated patient population. These data were reported at the American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting on Lymphoma Biology.

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Epizyme’s Independent Data Monitoring Committee confirmed that futility has been surpassed in four of the five study cohorts: diffuse large B-cell lymphoma (DLBCL) with Germinal Center B-cell (GCB) subtype and EZH2 mutations; DLBCL with GCB subtype and wild-type EZH2; DLBCL with non-GCB subtype; and, follicular lymphoma (FL) with EZH2 mutations. The fifth cohort enrolling patients with FL with wild-type EZH2 is ongoing, but has not yet reached futility assessment. The primary endpoint of the Phase 2 study is overall response rate1, and secondary endpoints include progression-free survival and duration of response.

"Patients with relapsed or refractory NHL are often faced with limited treatment options, particularly those who are highly refractory or whose disease is multiply relapsed as we have seen in this study population," said Franck Morschhauser, M.D., Ph.D., Centre Hospitalier Régional Universitaire de Lille, France, and primary investigator on the Phase 2 study. "These patients are in need of new therapeutic options, and while these data are early, we are encouraged and look forward to further understanding the impact that tazemetostat could have on patients as the trial proceeds."

Trial enrollment is on track and consistent with incidence rates for NHL subtypes, with approximately 20% of enrolled DLBCL GCB and FL patients having EZH2 mutations. As of the data cutoff2, 82 patients across all five study arms were evaluable for safety. Efficacy has been assessed on 47 evaluable patients from the four cohorts confirmed to have surpassed their pre-specified futility hurdles. The non-evaluable patients include 16 patients in the arms that have surpassed futility that are too early for efficacy evaluation or for whom data are not yet entered and 19 patients from the fifth cohort who have FL with wild-type EZH2.

Tazemetostat has demonstrated a favorable safety profile in all patients treated, consistent with the experience observed in the Phase 1 trial. The majority of adverse events were grade 1 or grade 2 within the 82 safety-evaluable patients. The most common treatment-related adverse events (≥5%) were nausea, asthenia, thrombocytopenia, neutropenia and fatigue, of which seven were grade 3 or higher. All adverse events resulted in low rates of both dose reductions (4%) and dose discontinuations (6%).

Among the 47 efficacy-evaluable patients, both objective responses (complete responses (CR) and partial responses (PR)) and stable disease (SD) have been observed. In the Phase 1 experience, Epizyme observed responses that evolved over time from SD to PRs and CRs. At data cutoff, best responses across the four cohorts were as follows:

DLBCL with GCB subtype and EZH2 mutations (n=5): one PR and two SD;
DLBCL with GCB subtype and wild-type EZH2 (n=19): two CRs, one PR and six SD;
DLBCL with non-GCB subtype (n=20): two CRs, four PRs and five SD; and,
FL with EZH2 mutations (n=3): three PRs.
All of the patients who have achieved a CR and the majority of patients who have achieved a PR or SD as best response are still on tazemetostat treatment as of the data cutoff.

"We are pleased by the performance of tazemetostat in the Phase 2 trial so far, which has been consistent with our Phase 1 results," added Peter Ho., M.D., Ph.D., Executive Vice President and Chief Medical Officer, Epizyme. "We have observed patients receiving clinical benefit from tazemetostat and continue to believe that prolonged exposure to treatment has the potential to result in decreased tumor burden over time."

Epizyme is continuing to enroll patients in its ongoing Phase 2 study in patients with NHL, as well as in two clinical trials in patients with certain genetically defined solid tumors.

A slide presentation of the early Phase 2 data of tazemetostat in NHL is available for download on the company’s website.

On July 17, 2016 Cell Medica, a leader in developing, marketing and manufacturing cellular therapeutics for cancer and infections, reported a ground-breaking co-development partnership with Baylor College of Medicine (Baylor) to develop next-generation technologies for engineering immune cells with enhanced functions for the treatment of solid tumors (Press release, Cell Medica, JUN 17, 2016, View Source [SID1234527733]). The collaboration provides Cell Medica with an exclusive license over several Baylor cell and gene technologies and an option to license new products introduced into the co-development partnership by Baylor’s leading research teams in the field of genetically engineered immune cells.

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Next generation technology

The collaboration will build on the recent clinical success of advanced chimeric antigen receptors (CARs) to enable human immune cells to recognize and kill cancer cells expressing tumor-associated antigens. The development plan will apply the CAR technology to natural killer T (NKT) cells as a novel immune cell type with biological properties that may be particularly effective for targeting solid tumors. NKT cells are known to infiltrate tissues where solid tumors arise and kill both malignant cells and cancer-enabling cells such as tumor-associated macrophages. The development plan also includes a genetically engineered T cell receptor (TCR) for use in NKT cells and T cells. The next-generation product concepts will combine the targeting aspects of CAR and TCR technologies with functional engineering to enable the modified immune cells to counteract the powerful inhibitory mechanisms that tumor cells deploy to evade the immune response. Cell Medica expects the collaboration to generate a significant number of new products for its cellular immunotherapy pipeline.

Co-development structure

The collaboration will accelerate the pioneering work of Dr. Leonid Metelitsa, Professor of Paediatrics – Oncology, with CAR-modified NKT cells. In published research, Metelitsa and his team have shown the potential therapeutic advantages of functionally enhanced CAR-modified NKT cells in pre-clinical cancer models. Metelitsa’s research team is part of Texas Children’s Cancer Center and the Center for Cell and Gene Therapy (CAGT) at Baylor College of Medicine, Texas Children’s Hospital and Houston Methodist Hospital. The CAGT has more than 20 years of experience working with genetically modified immune cells for the treatment of cancer and has conducted more than 40 clinical studies investigating cellular immunotherapies for the treatment of cancer.

Within the co-development structure, Baylor will conduct the pre-clinical and Phase I clinical research under the guidance of the Joint Steering Committee including members from both organizations. Cell Medica will work in parallel to support early product development and will use its substantial experience in manufacturing clinical-grade cell therapies since 2008 to establish robust production processes suitable for industrial scale-up. Following completion of successful Phase I studies, the products will transfer to Cell Medica for later-stage clinical development and commercialization.

The co-development funding will be available to research teams at Baylor with respect to new technologies, which may be utilized to create therapeutic products using modified NKT cells and other immune cells or to improve manufacturing systems. Baylor’s Innovation Development Center (IDC), led by Andrew Wooten, helped to structure this unique co-development partnership and will be responsible for Baylor’s alliance management function. As part of these responsibilities, the IDC will identify complementary technologies from ongoing Baylor research programs that may be included within the co-development plan.

Five product programs have been defined for the initial development plan in addition to a general process technology program. The preclinical development work for two of these programs will be executed by Drs. Gianpietro Dotti and Barbara Savoldo at the Lineberger Comprehensive Cancer Center, University of North Carolina. The Joint Steering Committee for the collaboration will review new product opportunities on a regular basis.

The co-development partnership builds upon the ongoing successful collaboration between Baylor and Cell Medica, supported by the Cancer Prevention and Research Institute of Texas (CPRIT), to develop baltaleucel-T for the treatment of a range of cancers associated with the oncogenic Epstein Barr virus.

License, Option and Co-development Arrangements

Cell Medica has entered into a License and Option Agreement for two platform patents related to engineered NKT cells, three target cancer antigens for CAR-modified NKT cells and a T cell receptor (TCR) technology. In addition, Baylor and Cell Medica have signed a co-development agreement under which Cell Medica will fund research aimed at new products as well as concepts/technologies in both oncology and non-oncology applications. Cell Medica will have an exclusive option to license future products within the co-development plan. Cell Medica has paid an up-front fee for the exclusive licensing arrangements and will make additional payments to exercise its exclusive option to license future products. Baylor is eligible to receive further payments related to late-stage clinical, regulatory approval and sales milestones, as well as single digit royalties for the successful development of specific products. As part of the up-front consideration, Baylor will receive Cell Medica Preference Shares, which are convertible into Common Shares. Specific financial terms have not been disclosed.

"We are very pleased to partner with Cell Medica in a collaboration aimed at unlocking the huge potential of cellular immunotherapy for the benefit of cancer patients," said Dr. Adam Kuspa, senior vice president and dean for research at Baylor College of Medicine. "The co-development partnership represents a novel aspect of this collaboration which will fully engage Baylor in the early stage development work, including Phase I studies".

"This collaboration with Baylor College of Medicine will place Cell Medica at the forefront of new product concepts for CAR-modified immune cells," noted Gregg Sando, CEO of Cell Medica. "Baylor’s leading research capability in this field should add significantly to our pipeline of high value products targeting cancer types that do not respond to conventional treatments."

On June 15, 2016 Cellectar Biosciences, Inc. (Nasdaq:CLRB) ("the company"), an oncology-focused biotechnology company, reported the results of a preliminary tumor-targeting study that shows its prototype paclitaxel chemotherapeutic conjugate, CLR 1602, may be up to 30 times more tumor selective in comparison to free paclitaxel (Filing, 8-K, Cellectar Biosciences, JUN 17, 2016, View Source [SID:1234513452]).

The preliminary in vivo study demonstrated that tumor uptake of CLR 1602’s paclitaxel payload increased by more than 30-fold over free paclitaxel, and also displayed an extended plasma half-life relative to free paclitaxel. The extended plasma half-life may, in part, explain the enhanced tumor uptake. Unlike free paclitaxel, which was rapidly cleared from plasma within 24 hours, CLR 1602 displayed prolonged retention even at 96 hours.

"The study results are a significant signal in the development of our paclitaxel Phospholipid Drug Conjugates (PDCs). More importantly, it represents further validation of our entire CLR CTX program," said Jim Caruso, president and CEO of Cellectar Biosciences. "These data clearly confirm our ongoing assertion that delivery of chemotherapeutics with our PDC platform may provide superior tumor cell targeting than chemotherapeutics alone, converting non-targeted chemotherapeutics into targeted cytotoxic agents. We anticipate conducting future studies and evaluating against other comparators, such as Abraxane."

The study was designed to assess the pharmacokinetics, absorption, and distribution after a single intravenous administration of CLR 1602, (N=24) a paclitaxel PDC vs. free paclitaxel (N=24) in tumor bearing mice. In this biodistribution study, CLR 1602, a paclitaxel Cremophor EL-free formulation (formulated without Cremophor, which is believed to contribute to free paclitaxel adverse event profile), was compared to free paclitaxel at equivalent sub-therapeutic concentrations in an effort to demonstrate enhanced CLR 1602 tumor targeting vs. free paclitaxel.

"This promising new in vivo paclitaxel data further confirms the tumor targeting selectivity of our PDC carrier, which has been consistently observed with oncology therapeutics and imaging agents. With targeting confirmed we will now optimize the PDC linker with the aim of enhancing the cytotoxic impact on cancer cells," said Jamey Weichert, Ph.D., founder and chief scientific officer of Cellectar Biosciences. "Furthermore, these results validate our ‘tool kit’ concept whereby carbon-14 labeled versions of our PDCs are utilized to quickly assess the potential tumor targeting enhancement that our PDC delivery system may afford to existing or new chemotherapeutic agents."

These quantitative results comparing biodistribution of CLR 1602 vs. free paclitaxel will be the subject of a poster presented at the 35th National Medicinal Chemistry Symposium in Chicago, June 26-29. The company also anticipates further data to be presented at another conference later this year.

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On June 17, 2016 Scancell Holdings Plc, (AIM:SCLP), the developer of novel Immunotherapies for the treatment of cancer, reported that it is suspending dosing with the current clinical trial supplies of SCIB1 with immediate effect (Press release, Scancell, JUN 17, 2016, View Source [SID:1234513447]).

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Ongoing quality control analysis has revealed that the stored drug product is no longer within the original specification. In discussion with the MHRA Clinical Trials Unit, and with patient safety of primary importance,
the Company has concluded that it is no longer suitable for further use, although no new side effects have emerged.

The suspension of dosing affects eight patients in the long term extension arm of the Phase 1/2 trial, SCIB1- 001 (out of the 35 patients that have been dosed), investigating SCIB1 as a monotherapy for the treatment
of melanoma. All study investigators have been informed and their patients will be notified as soon as possible.

SCIB1-001 was originally started in 2010 with a prospectively planned treatment period of only six months. However, continuing encouraging results and an excellent side effect profile led to successive amendments
to the clinical trial protocol to investigate increasing doses of the drug and eventually to examine a long term dosing regimen. As a result, some of the trial materials have now been stored for over 7 years.

The Company is planning to make a fresh batch of SCIB1 and has recently signed an agreement with a new GMP manufacturer. The primary reason for this is to support a new study of SCIB1 in combination with a
checkpoint inhibitor, as previously announced. However, the Company also intends to make this material available to patients currently in the long term extension of SCIB1-001 who wish to continue receiving the
drug. While it is expected that there will be a delay of approximately 9-12 months before the new SCIB1 material will be available for clinical use, it is anticipated that the anti-tumour response induced by SCIB1 should persist and eliminate any remaining tumour cells. Further doses of SCIB1 have been given for added protection to ensure the immune cells continue to patrol for any emerging cancer cells; subsequent administration of the new SCIB1 material should reactivate these memory immune cells to eliminate any recurring tumours.

Prof Poulam Patel, Chief Investigator for the SCIB1-001 clinical trial and Professor of Clinical Oncology at the University of Nottingham commented: "Results from the SCIB-001 trial to date have been very
encouraging and SCIB1 clearly warrants further investigation as a potential treatment for melanoma.

However as patient safety is our primary concern, the deterioration of stored clinical trial material from the original specification necessarily means that dosing of SCIB1 must be suspended until new drug product
becomes available."

Dr Richard Goodfellow, CEO of Scancell added: "Patient safety has always been our primary responsibility. Although we have seen no new adverse events it is unfortunate, but nevertheless appropriate, that we
suspend dosing of SCIB1 at this time while we work as quickly as possible to secure new supplies of this promising potential treatment for melanoma. Starting further efficacy studies with SCIB1 is only possible due to the results we have seen so far in the long-running SCIB1-001 study and we would again like to convey our thanks to the patients in that trial for their participation and support over the past 6 years."

On June 17, 2016 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported that a case study report from an ongoing clinical phase 2a study with its proprietary drug candidate MOR208 in patients with different subtypes of relapsed or refractory non-Hodgkin’s lymphoma (NHL) has been published in the Journal of Medical Case Reports (Press release, MorphoSys, JUN 17, 2016, View Source [SID:1234513435]).

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The case report shows that 3rd line monotherapy with the anti-CD19 antibody MOR208 has resulted in an ongoing complete response (CR), of currently more than 26 months’ duration, in a patient suffering from a morphological variant of diffuse large B-cell lymphoma (DLBCL). DLBCL – an aggressive type of blood cancer where B cells from the body’s immune system become malignant – is the most common form of NHL. As further reported, quality of life and performance status of the patient have remained high under MOR208 therapy, as evaluated by WHO grade 0 and Karnofsky score of 100%. MOR208 could be administered on an out-patient basis. Before being enrolled in the study with MOR208, the patient had a very dismal prognosis after early relapse to two prior lines of treatment, both including chemotherapy in combination with an anti-CD20 therapy with rituximab.

"Patients with NHL, who are refractory or show early relapse after previous therapies containing anti-CD20 treatment, have very limited treatment alternatives and usually a very poor prognosis. This reported case is one out of several examples of heavily pre-treated blood cancer patients showing long-lasting and still ongoing complete responses under anti-CD19 treatment with MOR208. This further encourages us to develop MOR208 as a potential new therapy for patients suffering from B cell malignancies, in particular DLBCL, in phase 2 combination studies," said Dr. Arndt Schottelius, Chief Development Officer of MorphoSys AG.

As previously reported, in the DLBCL subgroup overall response rate (ORR) was 36% (based on evaluable patients). In DLBCL, median duration of response (Kaplan-Meier estimates) was 20 months with three ongoing responses of up to more than 26 months. Patient evaluation and data analysis of the clinical phase 2a trial are ongoing. 92 patients were enrolled in the trial.

The full article published in the Journal of Medical Case Reports 2016 can be found here.

Further details of the case report
The patient, a 33 year-old male suffering from T-cell/histiocyte-rich large B-cell lymphoma, a morphological variant of DLBCL, had previously experienced early relapses after both, first-line treatment with rituximab combined with chemotherapy (R-CHOP) (relapse after 5 months) and second-line salvage chemotherapy including rituximab consolidated with an autologous stem-cell transplant (relapse after 6 months). Subsequently, the patient has been enrolled in the phase 2a trial of single-agent MOR208. In the study, the patient was treated for 12 weeks with 12mg/kg MOR208, administered intravenously once a week, followed by an ongoing maintenance therapy with administration of MOR208 every second week. Three months after starting 3rd line treatment with MOR208, the patient PET-CT assessments demonstrated a partial response (PR). Nine months later, during the ongoing maintenance therapy, PET-CT confirmed a complete response (CR). As stated in the case report, the patient experienced only few adverse events, which were all limited to infections of the respiratory tract. The quality of life and performance status of the patient has remained high during treatment, as measured by WHO grade 0 and Karnofsky score of 100%, with MOR208 treatment being administered on an out-patient basis. The patient’s complete response is ongoing, with a current duration of more than 26 months (24 months duration at the time of manuscript acceptance). The full article published in the Journal of Medical Case Reports 2016 10:123 can be found here.

About MOR208
MOR208 is an anti-CD19 antibody with a proprietary modification to the Fc portion in clinical development to treat B cell malignancies.

An open-label, phase 2a, multicenter study was designed to assess the activity and safety of weekly doses of 12 mg/kg MOR208 as a single agent in 92 pre-treated patients with various subtypes of relapsed/refractory NHL patients including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and other indolent NHL (iNHL) including follicular lymphoma (FL). All patients had received at least one prior rituximab-containing therapy. According to the data observed, MOR208 showed a low level of infusion reactions. According to a subgroup analysis data presented at the ASCO (Free ASCO Whitepaper) 2016 annual meeting, a disease control rate (CR + PR + SD) of 40% in DLBCL and 73% in iNHL patients was observed. Progression-free survival (PFS) with MOR208 therapy was shown to be comparable in rituximab refractory and non-refractory NHL patients (median PFS 5.3 versus 6.6 months, HR 0.85, 95% CI 0.45-1.6, p=0.59) thus demonstrating in this trial an activity of MOR208 independent of the response to a prior anti-CD20 therapy. Updated data for the overall trial population furthermore revealed that after 12 months the PFS rate was 40% in both DLBCL and iNHL patients. Nine patients treated with MOR208 were still in remission (7 CRs, 2 PRs), the longest responses currently ongoing for 26 months. The overall response rate (ORR) of MOR208 reached 36% in the DLBCL subgroup and 33% in iNHL patients (both based on evaluable patients). Based on all patients with DLBCL and iNHL in the study, the ORR was 26% and 29%, respectively.

In April 2016, the first patient was dosed in a phase 2 combination trial (L-MIND study) investigating safety and efficacy of MOR208 in combination with lenalidomide in 80 patients with relapsed or refractory DLBCL. Furthermore, MorphoSys in 2016 plans to start the safety part of a clinical trial evaluating MOR208 in combination with the chemotherapeutic agent bendamustine in DLBCL which is intended to lead into a pivotal study to start in 2017. In addition, at the ASCO (Free ASCO Whitepaper) 2016 Annual Meeting the trial design of a phase 2 study with MOR208 was presented which trial is planned to evaluate MOR208 in combination with idelalisib in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) in patients no longer responding to or no longer tolerating Bruton’s tyrosine kinase (BTK) inhibitor therapy (e.g. ibrutinib). After the discontinuation of several combination trials of idelalisib with other compounds, this planned trial is currently under review and discussions with regulatory authorities are ongoing. MorphoSys is currently exploring alternative study designs to evaluate MOR208 in a combination trial in CLL/SLL patients previously treated with a BTK inhibitor.