Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy.
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ADCs: A booming field for new cancer-fighting therapies

ADCs: A booming field for new cancer-fighting therapies | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
Six years after the first antibody-drug conjugate (ADC) was pulled from the market, the pipeline is once again filled with an array of potent new treatment candidates. The reach of commercially available ADCs is also expanding rapidly, making the technology particularly attractive to companies large and small. 

At last count, there were more than 50 of the drugs in development, up from the 30-some being worked on in 2014. 

"Of those 50-odd [ADC] clinical candidates in development, 12 integrate ImmunoGen technology," ImmunoGen CEO Mark Enyedy said in an interview. "Eight are being developed by our partners, and four are being developed by ImmunoGen … so we have a large presence in the market."

ADCs seek to deliver highly potent doses of cytotoxins directly to tumors in a way that avoids many of the side effects of chemotherapy on healthy cells. The technology has three components: monoclonal antibodies attached to cancer-killing drugs by chemical linkers. Most ADC efforts center around various cancers, but research is starting to extend further into other disease areas as well.

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Juno's JCAR017 shows positive effect in early-stage DLBCL study

Juno's JCAR017 shows positive effect in early-stage DLBCL study | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
A Phase 1 clinical trial, TRANSCEND, assessing Juno Therapeutics' ([[JUNO]] -0.9%) JCAR017 in patients with relapsed/refractory diffuse large B cell lympho
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Biomunex appoints Dr. Amigorena and Dr. Grabulovski as key scientific and strategic advisors 

Biomunex appoints Dr. Amigorena and Dr. Grabulovski as key scientific and strategic advisors  | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
Biomunex Pharmaceuticals, a biopharmaceutical company pioneering a new class of bispecific antibody therapeutics based on its proprietary BiXAb® platform, today announces the appointments of Dr. Sebastian Amigorena as key scientific advisor and Dr. Dragan Grabulovski as key strategic advisor.

The new appointees will help the company reach its strategic objective to become a leader in bispecific antibody therapeutics development for immuno-oncology. Dr. Amigorena’s experience and his cutting-edge research in the area of cancer immunology together with Dr. Grabulovski’s expertise in bispecific antibody development and in building commercially successful biotechnology companies will help Biomunex to rapidly advance towards its corporate objective. Both experts were attracted by the opportunity to join the biopharmaceutical company to help leverage its proprietary next-generation ‘Plug-and-Play’ BiXAb bispecific antibody platform for the development of highly potent immunotherapeutics.

“Biomunex’ BiXAb platform is perfectly positioned for the identification and development of innovative clinical candidates that exploit the powerful anti-cancer biology of immune checkpoint inhibitors,” said Dr. Amigorena.

“I am impressed by the excellent biophysical properties and the potential of the ‘Plug-and-Play’ aspect of the BiXAb bispecific antibody technology platform,” said Dr. Grabulovski. “I am genuinely looking forward to contributing to the further development of this exciting company by helping Biomunex reach its strategic objectives and create an innovative portfolio of clinical product candidates.”

“We are very pleased to welcome Dr. Amigorena and Dr. Grabulovski as key advisors,” said Dr. Pierre-Emmanuel Gerard, chief executive officer of Biomunex Pharmaceuticals. “As international key opinion leaders they will play an instrumental role as we advance our first oncology programs into pre-clinical and clinical development.”
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Significant Barriers to Clinical Implementation of Tumor Profiling | OncoTherapy Network

Significant Barriers to Clinical Implementation of Tumor Profiling | OncoTherapy Network | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
The clinical implementations of tumor profiling may be even greater than previously recognized. However, large-scale cancer gene profiling while feasible still faces significant barriers. Researchers leading the largest genomic tumor profiling effort of its kind say such studies are technically feasible in a broad population of adult and pediatric patients with many different types of cancer. 

While determining the genetic makeup of a patient’s tumor is a critical tool for precision cancer medicine, there are still several challenges and unanswered questions about large-scale clinical application of the methods. Just over half of patients in the study who gave consent and had tumor profiling ordered by a physician actually received results, due to a variety of technical and logistical factors.

Published online by JCI Insight, it is the first report of clinical implementation of tumor profiling in an enterprise-wide, unselected cancer patient population. The report contains data on 3,727 patients whose samples were analyzed during the first year of the Profile program at Dana-Farber/Brigham and Women’s Cancer Center and Boston Children’s Hospital.  “A widespread genomic profiling initiative is expensive, and this cost has been borne by our institutions,” said study author Laura MacConaill, PhD, who is the scientific director of the Profile program and with the Dana-Farber Cancer Institute and Brigham and Women’s Hospital (BWH).

In approximately 10% of cases, the test information was used in caring for the patient. Reasons for the attrition rate included absence of effective drugs, timing of genomic testing in the course of a patient’s disease, less than optimal access to targeted drugs or clinical trials, and patient and provider preferences.

Identifying these barriers allows researchers to develop and implement new solutions, with the goal of improving the rate of use of the genomic results. Overall, the turnaround time from receiving the sample to issuing a report of the findings was 5.3 weeks, a timespan the researchers said they have since shortened to less than 3 weeks.
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Novartis says 82 percent of leukemia patients in remission after CAR-T

Novartis says 82 percent of leukemia patients in remission after CAR-T | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
An experimental cancer therapy being developed by Novartis AG eliminated an aggressive form of blood cancer in 82 percent of children and young adults treated with modified immune cells in a mid-stage trial, the company said on Saturday.

Interim results from the multi-center trial for 50 patients with acute lymphoblastic leukemia whose cancer returned or did not respond to other treatment, showed that 41 were disease-free three months after treatment with the drug, called CTL019.

The trial results were presented at a meeting of the American Society of Hematology in San Diego.

Novartis estimated that 60 percent of those responders were relapse-free after six months. Complete remission was defined as including "remission with incomplete blood count recovery."

CTL019 is part of an experimental class of drugs that are made by genetically altering a patient's T-cells, a type of white blood cell, in the lab to help the immune system find and kill cancer cells. The modified cells, called chimeric antigen receptor T-cells, or CAR-T, are infused into the patient.

Novartis said it plans to file early next year for U.S. Food and Drug Administration approval of CTL019.

The company said nearly half of trial patients experienced severe cytokine release syndrome, a dangerous buildup of toxic debris known as CRS, and 15 percent experienced serious neurological problems including delirium. Researchers said the side effects were treated, and no patients died due to CRS.

CRS, a known side effect of CAR-T therapy, led to the decision last week to halt a trial of JCAR015, a rival drug being developed by Juno Therapeutics Inc.

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The epigenetic landscape of T cell exhaustion

The epigenetic landscape of T cell exhaustion | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
Exhausted T cells in cancer and chronic viral infection express distinctive patterns of genes, including sustained expression of programmed cell death protein 1 (PD-1). However, the regulation of gene expression in exhausted T cells is poorly understood. Here, we define the accessible chromatin landscape in exhausted CD8+ T cells and show that it is distinct from functional memory CD8+ T cells. Exhausted CD8+ T cells in humans and a mouse model of chronic viral infection acquire a state-specific epigenetic landscape organized into functional modules of enhancers. Genome editing shows that PD-1 expression is regulated in part by an exhaustion-specific enhancer that contains essential RAR, T-bet, and Sox3 motifs. Functional enhancer maps may offer targets for genome editing that alter gene expression preferentially in exhausted CD8+ T cells.
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bluebird bio Announces Interim Phase 1 Dose Escalation Data for its Anti-BCMA CAR T Product Candidate in Patients with Relapsed/Refractory Multiple Myeloma 

bluebird bio Announces Interim Phase 1 Dose Escalation Data for its Anti-BCMA CAR T Product Candidate in Patients with Relapsed/Refractory Multiple Myeloma  | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies for cancer, announced that interim data from its ongoing Phase 1 clinical study of bb2121, the company’s investigational anti-BCMA CAR T cell product candidate in patients with relapsed/refractory multiple myeloma, will be presented on Thursday, December 1, 2016 at the 28th EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium in Munich, Germany. bluebird bio is developing bb2121 in collaboration with Celgene Corporation.

“We are pleased that these early data from our ongoing Phase 1 study of bb2121 demonstrate objective anti-tumor responses in heavily pre-treated patients with multiple myeloma, with all patients in the 15.0 x 107 and 45.0 x 107 CAR+ T cell dose cohorts achieving responses, including among them, patients with stringent complete responses and elimination of minimal residual disease,” said David Davidson, M.D., chief medical officer, bluebird bio. “We are also encouraged by the safety profile to date, particularly the lack of severe cytokine release syndrome or neurotoxicity. In light of these positive data, and thanks to the multiple participating clinical sites and centralized manufacturing infrastructure we and our partner Celgene have built for this program, we anticipate efficiently completing the dose escalation stage of the trial and initiating the expansion cohort.”
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New Hope for Antibiotic Resistance in East Africa

New Hope for Antibiotic Resistance in East Africa | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
By 2050 an estimated 10 million people will die each year from antibiotic-resistant infections -- almost 90% of those in the developing world. To address this, Phages for Global Health is teaching scientists in East Africa how to develop cheap, naturally occurring antibiotic alternatives (phages) that are effective against antibiotic-resistant bacteria. Phages have been used successfully against problem bacteria for >100 years in certain regions, but they have not yet been applied in Africa.
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French cancer specialist Innate Pharma can remain independent, for now: CEO

French cancer specialist Innate Pharma can remain independent, for now: CEO | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
France's Innate Pharma believes that its cash position and portfolio are sufficiently robust for the cancer drug company to remain independent for the time being and will seek co-development deals modeled on an agreement struck with AstraZeneca in April.

Innate sees its independence as key to delivering optimum shareholder value in a sector characterized by big-money deals as large drugmakers look to acquire new, effective cancer treatments. In August Pfizer announced the $14 billion purchase of Medivation Inc, adding its blockbuster prostate cancer drug Xtandi to a growing oncology portfolio.

Marseille-based Innate specializes in immuno-oncology, a new therapeutic field that has attracted investors' attention with drugs that stimulate or take the brakes off the body's immune system to recognize and kill cancer cells.

Big pharma groups such as Bristol-Myers Squibb, Merck, Roche and AstraZeneca are leading the immunotherapy pack, but smaller rivals have also been active in the field.

Innate's share price has risen by more than 30 percent over the past month after positive preliminary data for trials involving the combination of Lirilumab, a human monoclonal antibody, with Bristol Myers Squibb's (BMS) Opdivo in solid tumor's of the head and neck.

The two companies, which teamed up in 2011, have other trials in the works and are hopeful that the combination will prove beneficial for patients suffering other forms of cancer.
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Cancer vaccines market will triple to $7.5B by 2022, report says 

Cancer vaccines market will triple to $7.5B by 2022, report says  | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
Two big reasons for the immunotherapy combo approach to cancer treatment? Drug resistance and side effects that come along with older treatments. And though checkpoint inhibitors may be the stars of today's treatment show, previously disappointing cancer vaccines are playing a resurgent role.

Though cancer vaccines have fallen short in clinical trials in recent years, the global market for these products—as crucial pieces of immunotherapy regimens—will likely grow to $7.5 billion in 2022 from $2.5 billion in 2015. That's a compound annual growth rate of nearly 17%, a new report from GBI Research predicts.

A 2015 report by Infiniti Research predicted a higher growth rate of more than 27% through 2019.

Why is GBI Research so optimistic about cancer vaccines? First, more than 1,200 products are under development, and they make up almost 17% of the entire oncology pipeline. That's the largest of any therapy area, analyst Adam Bradbury said in a statement.

Plus, cancer R&D as a whole is growing rapidly, as a recent report by BioPharm Insight shows. Counting only studies initiated by contract research organizations, 827 cancer trials started in the third quarter of this year, up from 671 for the same period last year.

The new report by GBI Research suggests that new CAR-T immunotherapies from Novartis (tisagenlecleucel-T) and Kite Pharma (KTE-C19) will reach blockbuster status by 2022, if approved.
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Roche forms 21-site I/O R&D network, commits $100M

Roche forms 21-site I/O R&D network, commits $100M | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
Roche has put together a cancer immunotherapy research network and committed up to $100 million to support collaborations between the 21 academic centers. Members of the network will share data, expertise and technology with a view to accelerating the progress of programs out of the lab and into the clinic.

The network, dubbed the global cancer immunotherapy Centers of Research Excellence (imCORE), formalizes the links between Roche, Genentech and the academic centers. Roche is hoping linking and supporting the research sites will lead to new ideas about how to increase the proportion of patients who respond to cancer immunotherapies. So far, the effects of immunotherapies on tumors have ranged from very powerful to non-existent.

Roche is looking outside its walls for help solving the problem.

“We believe the fastest way to advance progress against cancer is through collaboration, and consistent with our values, the goal of imCORE is to facilitate access to new technologies and emerging data among the top researchers around the world,” Roche CMO Dr Sandra Horning said in a statement.

The Swiss Big Pharma is putting up $100 million to support collaborations within the network. That sum, while tiny in the context of Roche’s $8 billion biopharma R&D budget, is meaningful for the type of projects being pursued within imCORE. The sweet spot for the network spans from basic research, through preclinical and into human studies. Roche plans to maximize the bang for its buck by pooling and sharing data generated by imCORE projects.

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Bristol-Myers' Opdivo nets the first PhIII gastric cancer win for checkpoint inhibitors | FiercePharma

Bristol-Myers' Opdivo nets the first PhIII gastric cancer win for checkpoint inhibitors | FiercePharma | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
Bristol-Myers Squibb’s Opdivo may have recently struck out as a monotherapy for non-small cell lung cancer patients. But it’s hardly lacking for ways to expand, and it proved that Thursday in a Phase III gastric cancer trial.

Among chemo-intolerant patients or those who failed to respond to chemo, the checkpoint inhibitor topped placebo at extending overall survival, the company said. BMS’ partner, Japan’s Ono Pharmaceutical, conducted the trial in Japan, Korea and Taiwan.

It’s a win for Opdivo, which is the first drug in its class to show a survival benefit in stomach cancer patients. If it can eventually snag an indication there--and beat its immuno-oncology rivals, Merck’s Keytruda and Roche’s Tecentriq, to the therapy area--it’ll have a wide-open shot at a sizable market; gastric cancer is the third leading cause of cancer-related death in the world, killing more than 720,000 patients each year.
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Safety Data from a First-in-Human Phase 1 Trial of NKG2D Chimeric Antigen Receptor-T Cells in AML/MDS and Multiple Myeloma

Safety Data from a First-in-Human Phase 1 Trial of NKG2D Chimeric Antigen Receptor-T Cells in AML/MDS and Multiple Myeloma | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
Conventional CAR-T cells express a single chain antibody variable fragment that restricts recognition to one tumor antigen and a limited set of cancers.  This study employs a novel CAR fusing full-length human NKG2D with the CD3z signaling domain.  In autologous transduced CM-CS1 T cells, NKG2D CAR receives endogenous costimulation via DAP10 to target multiple NKG2D-ligands that are upregulated in solid and hematologic malignancies but absent or poorly expressed on healthy tissues.  

Methods: A phase 1 dose-escalation study to establish safety and feasibility of a single infusion of CM-CS1 T cells without lymphodepleting conditioning enrolled subjects with AML/MDS-RAEB or relapsed/refractory progressive multiple myeloma (MM) without standard therapy options (NCT02203825).  Eligibility criteria included suitable organ function, no CNS disease, no prior allogeneic SCT or adoptive T-cell therapy, no therapy within 3 weeks prior to infusion, no immune suppression, and no uncontrolled infection.  Dose-escalation spanned 4 cohorts [half-log increments from 1x106 to 3x107 CM-CS1 T cells] according to a 3+3 design.  DLTs included ≥ Grade 3 non-hematologic toxicity or ≥ Grade 2 autoimmune toxicity related to CAR T cells.  Initial assessment was at 28 days.   At least 1 AML/MDS and 1 MM subject were mandated in each dose level.  Manufacturing included PBMC stimulation with OKT3 and IL-2 followed by 2 rounds of retroviral transduction at DFCI’s Cell Manipulation Core Facility.  Vector copy number (VCN) and replication-competent retrovirus (RCR) testing were performed on whole blood and PBMCs, respectively, using quantitative PCR.

Results:  From April 2015 to July 2016, 11 subjects were infused, and 10 completed the DLT period.  Eight of 11 were male, 6 had AML/MDS, and median age was 70 (range 44 to 79) (Panel A).  Median WBC was 2.3 (range 0.7 to 7.2 K/uL); median ALC was 0.74 (range 0.09-2.37 K/uL).  Five had cells manufactured from peripheral blood; 6 underwent apheresis.  Median percentage of blasts in bone marrow for AML/MDS patients was 50% (range 4-68%).  All myeloma patients had undergone ≥ 5 therapies including ≥1 autologous SCT.  Four of the 6 AML/MDS patients had secondary disease, 3 had complex cytogenetics, 3 had p53 mutations, and 1 had a FLT3-ITD mutation.

Dose-escalation proceeded from 1x106 to 3x107 CM-CS1 T cells.  All 11 products passed release criteria, and there were no infusion reactions.  Products consisted of median 97.2% CD3+ cells and 31.0% CD8+ cells, with vector-specific NKG2D expression on median 74.6% of CD3+ and 66.3% of CD8+ cells (Panel B).  The first 10 subjects completed their 28 day evaluation period without DLTs.  There were no cases of cytokine release syndrome, cell-related neurotoxicity, auto-immunity, or CAR T-related death.   SAEs included a Grade 4 intracochlear bleed and an episode each of grade 4 neutropenia and thrombocytopenia deemed related to disease progression.  Forty percent of patients experienced some Grade 3 toxicity, all related to underlying disease or a complication thereof (Panel C).
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Relapses Spell More CAR-T Uncertainty For Juno

Relapses Spell More CAR-T Uncertainty For Juno | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
After seeing multiple patient deaths Juno (NASDAQ:JUNO) is facing the likely discontinuation of its lead CAR-T asset, JCAR015. Today fresh troubles emerged with JCAR018, its highly promising anti-CD22 construct designed to treat patients who relapse after a CD19-directed CAR.

At Ash this morning the NCI’s Dr Terry Fry said a study of JCAR018 in ALL patients showed for the first time that the CD22 antigen can be lost, causing CAR-T patients to relapse for a second time; there has also been a death from sepsis. And Dr Fry cast doubt on JCAR018’s potential as a salvage treatment, proposing instead its use as an initial line of CAR therapy.

Of course, this does not mean that this is Juno’s policy, since Dr Fry is running his trial at the NCI at arm’s length. Juno had independently bought rights to JCAR018 from the private company Opus Bio for around $84m, and paid the sellers a $15m milestone after Dr Fry unveiled data in an initial seven patients at Ash 2015.

He provided a further update at this year’s AACR meeting, highlighting four complete remissions in nine patients given JCAR018, and a promising lack of neurotoxicity (The next CAR-T target generates promise and caution, April 25, 2016). That had put Juno in pole position as the most advanced developer of a CD22-directed CAR.

Complete remissions

Today at Ash those data were updated, with 16 patients now treated, and nine being put into complete remission, including eight of the 10 on the two highest cell doses.

However, only three of the ALL responders are still in remission, at between three months and over a year. Five relapses were seen at two to six months’ follow-up, and there was no update on one lymphoma patient who had responded.

Four of the relapsed patients had loss of the CD22 antigen, either completely or via what Dr Fry termed a “decrease in site density”. This is the first documented evidence in patients that CD22 antigen loss can occur – just as it does with CD19, though in the latter case the mechanism is different.

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Novartis Makes Its Case For Driving A CAR Into The Real World

Novartis Makes Its Case For Driving A CAR Into The Real World | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
Rather like Kite’s (NASDAQ:KITE) registrational Zuma-1 trial of KTE-C19 in lymphoma, Novartis’ (NYSE:NVS) Eliana study has generated a fileable response rate. In the case of the Swiss firm’s rival CAR-T therapy, CTL019, this is in childhood leukemia patients.

While safety has likely taken on fresh importance with the US FDA, Novartis confirmed that CTL019 would be submitted early next year, putting it neck and neck with Kite to bring the first CAR product to market. But perhaps underappreciated is Eliana’s demonstration that a complex autologous cell therapy has real-world potential, with one commercial site manufacturing product for three continents.

The University of Pennsylvania’s Dr Stephan Grupp, who presented the interim Eliana readout at Ash on Saturday, said the trial was the first of a CAR-T product to be truly global. It took in 25 hospitals at sites in North America, Europe and the Asia/Pacific region.

In contrast, Zuma-1 was limited to the US, but of course did comprise 23 sites. Dr Grupp said in Eliana CTL019 was produced at Novartis’s manufacturing facility at Morris Plains, New Jersey, and shipped to the various international sites, with site-specific training undertaken in logistics and patient management.

Investors are keen to see whether CAR-T manufacturing by a big pharma company, at commercial scale, can overcome academia’s production problems. Failure to produce the CAR has been as high as 26% previously, and Dr Grupp’s revelation that there were only five manufacturing failures in 81 patients enrolled will have brought added comfort.
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Promising results in trial of engineered T cells in high-risk leukemia

Promising results in trial of engineered T cells in high-risk leukemia | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
The 24 patients had undergone most standard therapies available to them and yet their chronic lymphocytic leukemia had come back strong. Almost all of them had been treated with a newly approved, targeted drug called ibrutinib; data from other studies show that most patients whose disease progresses after ibrutinib treatment do not survive long. The majority of the 24 had chromosomal markers in their leukemia cells that serve as[DAE1]  “predictors of a bad response to most standard therapies,” said Dr. Cameron Turtle of Fred Hutchinson Cancer Research Center.

But most of these patients, who were enrolled in a small, early-phase trial, saw their advanced tumors shrink or even disappear after an infusion of genetically engineered immune cells. Turtle, one of the study’s leaders, presented the results on Saturday at the 2016 annual meeting of the American Society of Hematology in San Diego.
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CD19-targeting CAR T-cell immunotherapy yields high responses in treatment-resistant CLL

CD19-targeting CAR T-cell immunotherapy yields high responses in treatment-resistant CLL | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
In a small, early phase trial, a high percentage of patients who had exhausted most traditional treatments for chronic lymphocytic leukemia saw their tumors shrink or even disappear after an infusion of a highly targeted, experimental CAR T-cell immunotherapy developed at Seattle's Fred Hutchinson Cancer Research Center.

Fred Hutch researchers will present their findings in an oral presentation at 7:45 a.m. Dec. 3 at the American Society of Hematology Annual Meeting and Exposition in San Diego.

Almost all of the 24 patients in the study had cancer that had advanced despite treatment with a newly approved drug called ibrutinib - an ominous indicator for patient survival. Most patients also had chromosomal markers in their leukemia cells that put them at high risk - "predictors of a bad response to most standard therapies," said Dr. Cameron Turtle, a hematologist/oncologist in the Clinical Research Division at Fred Hutch who co-leads the trial with colleagues Drs. David Maloney and Stanley Riddell.

Turtle's presentation will focus on the results in a subgroup of patients who received the CAR T-cell infusion using preferred chemotherapy and CAR T-cell doses that evolved from recent trial data. Fourteen of the 19 restaged patients experienced a partial or complete regression of the disease in their lymph nodes. Of the 17 who had leukemia in their marrow when they enrolled in the trial, 15 saw the marrow become cancer-free after receiving CAR T-cells.
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New data on risk vs benefit for potent CAR-T cancer drugs

New data on risk vs benefit for potent CAR-T cancer drugs | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
A promising but risky new group of customized cancer drugs will be in focus this weekend at the annual meeting of the American Society of Hematology (ASH), where clinical trial results will help clarify their potential for doctors and investors.

Experimental chimeric antigen receptor T-cells, or CAR-Ts, are made by genetically altering a patients' own T-cells in the lab to help the immune system find and kill cancer cells. The altered cells are then infused back into the patient.

Early excitement over the drugs has propelled investor interest in biotech Kite Pharma Inc, whose shares have tripled since a 2014 initial public offering, as well as rival Juno Therapeutics Inc, whose therapy JCAR015 has generated concerns after five leukemia patients died due to severe brain swelling. Juno shares now trade about 14 percent below their IPO price.

"Juno has dug themselves into such a deep hole," said Brad Loncar, manager of the Loncar Cancer Immunotherapy ETF. "My guess is that they may drop the JCAR015 program." He will be watching closely to see whether data at ASH on another Juno candidate, JCAR017, shows similar issues.
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Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade

Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
Therapeutic blocking of the PD1 pathway results in significant tumor responses, but resistance is common. We demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB) and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell inhibitory receptors. Both type I and II interferons maintain this resistance program. Crippling the program genetically or pharmacologically interferes with multiple inhibitory pathways and expands distinct T cell populations with improved function despite expressing markers of severe exhaustion. Consequently, tumors resistant to multi-agent ICB are rendered responsive to ICB monotherapy. Finally, we observe that biomarkers for interferon-driven resistance associate with clinical progression after anti-PD1 therapy. Thus, the duration of tumor interferon signaling augments adaptive resistance and inhibition of the interferon response bypasses requirements for combinatorial ICB therapies.
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Scoop: Emails between Apple and FDA hint at future plans

Scoop: Emails between Apple and FDA hint at future plans | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
Since its well-publicized meeting with the FDA in 2013, Apple has continued to meet with the agency regularly as well as to correspond by phone and email, according to emails obtained by MobiHealthNews via a Freedom of Information Act request to the FDA.
 
These emails show that Apple and the FDA have discussed the App Store review process, the 510(k) process, ResearchKit apps, diagnostic apps, working with the FDA in an “unregulated” way and more. The FDA even invited Apple to participate in regular briefings designed to help guide an international effort to harmonize medical software regulation. Though much of the sensitive information is redacted, the emails also point to three regulated medical devices that Apple is seriously pursuing: an app for diagnosing Parkinson’s disease and two separate but related cardiac devices.
 
Finally, the emails also suggest that, after Apple received a good deal of press for its 2013 FDA meeting, the agency worked with Apple to keep future meetings under the radar. The record shows meeting names and locations were changed, and great consideration was given to when to include top officials, like FDA Commissioner Dr. Robert Califf and Dr. Jeffrey Shuren, director for the agency’s Center for Devices and Radiological Health, whose calendars are public and might have exposed the company to more media scrutiny.
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Five Lessons From Today's Pharma Failures

Five Lessons From Today's Pharma Failures | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
Drug and biotech stocks might rise because of shifting political winds or the prospect of big acquisitions. But this morning was a reminder that the biggest challenge facing companies that seek to invent new medicines and prove they work remains biology itself.

Eli Lilly announced that solanezumab, its experimental drug for Alzheimer’s, failed to improve cognition in a large clinical trial. After repeated failures, Lilly is finally admitting defeat. Juno Therapeutics, a biotechnology company developing immune cells that hunt down and kill tumors, said that two patients had died in a clinical trial of one of its leukemia treatments.

Lilly shares traded down 11% to $67.94; Juno shares dropped 27% to $21.67. Here are some lessons from these failures. They’re all things drug developers know. But they’re also lessons that are all too easy to forget.

1. Be careful about the need for speed

Juno announced on July 7 that three patients had died in one of its clinical trials, blaming a drug it was administering with a cancer-killing cell treatment code-named JCAR015. The Food and Drug Administration bought that story. Now Juno has announced that two more patients have died. All the deaths have the same cause: swelling and bleeding in the brain. There’s a very good argument that Juno and the FDA moved too fast in trying to restart the studies.
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Juno Therapeutics Places JCAR015 Phase II ROCKET Trial on Clinical Hold

Juno Therapeutics Places JCAR015 Phase II ROCKET Trial on Clinical Hold | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
Juno Therapeutics Places JCAR015 Phase II ROCKET Trial on Clinical Hold
SEATTLE--(BUSINESS WIRE)--Nov. 23, 2016-- Juno Therapeutics, Inc. (Nasdaq: JUNO), a biopharmaceutical company focused on re-engaging the body’s immune system to revolutionize the treatment of cancer, today announced that it has voluntarily placed on hold the Phase II clinical trial of JCAR015 in adult patients with relapsed or refractory B cell acute lymphoblastic leukemia, known as the “ROCKET” trial. The clinical hold was initiated after two patients suffered cerebral edema earlier this week. One patient died and as of last night the other is not expected to recover.
Juno has notified the Food & Drug Administration of the voluntary hold and is working with the agency and the Data and Safety Monitoring Board to determine next steps. The company is assessing data from the cases and the trial and is evaluating its options regarding the JCAR015 program.
Juno’s trials and plans for its other CD19-directed CAR T cell product candidates, including JCAR017, are not affected.
Dominique Blanchard's insight:
Two patients already died in July in the same clinical trial. 
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Accès aux Médicaments : le classement 2016 des laboratoires pharmaceutiques 

Accès aux Médicaments : le classement 2016 des laboratoires pharmaceutiques  | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
L’Indice d’Accès aux Médicaments (Access to Medicines Index) 2016, publié lundi, établit un classement des 20 principaux laboratoires pharmaceutiques en fonction des efforts qu’ils accomplissent afin d’améliorer l’accès aux médicaments dans les pays à faibles et moyens revenus. GSK arrive en tête du classement pour la 5ème fois suivi par un groupe compact comprenant Johnson & Johnson, Novartis et Merck KGaA.
Cet indice est publié tous les deux ans par l’Access to Medicine Foundation, un organisme indépendant à but non lucratif financé par la Fondation Bill et Melinda Gates, le Ministère Néerlandais des Affaires Étrangères et le Département pour le Développement International du Royaume-Uni.
Cet indice classe les laboratoires « en fonction de leurs efforts d’amélioration de l’accès aux médicaments, l’évaluation portant sur sept domaines comportementaux. Il identifie les meilleures pratiques, met en lumière les domaines faisant l’objet d’améliorations et ceux dans lesquels des actions importantes restent nécessaires », précise l’Access to Medicine Foundation.
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Anti-PD1, CTLA-4 Immunotherapy-Related Neurotoxicities ‘Not Uncommon’ in Patients With Melanoma | OncoTherapy Network

Anti-PD1, CTLA-4 Immunotherapy-Related Neurotoxicities ‘Not Uncommon’ in Patients With Melanoma | OncoTherapy Network | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
Immune checkpoint inhibitor-related neurotoxicities are more frequent in clinical practice than clinical trials—particularly among patients receiving ipilimumab (Yervoy) plus nivolumab (Opdivo) combination therapy (ipi+nivo), according to a retrospective single-institution cohort study reported online in the Annals of Oncology.

“Neurologic toxicity is not uncommon, and may be more frequent in patients treated with combination ipi+nivo,” reported coauthor James Larkin, MD, of the Royal Marsden Hospital in London, and colleagues.

“A prompt and considered approach is required to optimize outcomes in this group of patients,” they concluded. “There is a risk of neurological irAEs [immunotherapy-related adverse events] at any stage throughout the course of treatment with immune-checkpoint agents, however presentations within the first four months predominated in our cohort (8/10, 80%).”

Small numbers prevented “any definitive statements,” but findings from the review suggest the possibility that neurotoxicity might predict treatment response, the team noted.

Immune checkpoint blockade with anti-PD1 and anti-CTLA-4 antibodies has “greatly improved” survival among patients with advanced melanoma and previously published clinical trial data suggests a cumulative neurotoxicity incidence of less than 1% among patients with melanoma receiving ipilimumab, nivolumab, or pembrolizumab (Keytruda) monotherapy, the researchers reported.

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CRISPR Targets Cancer in First Human Trial — What You Need to Know

CRISPR Targets Cancer in First Human Trial — What You Need to Know | Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy. | Scoop.it
On Tuesday June 21, an advisory panel from the National Institute of Health (NIH) green lighted a proposal to use the game changing technique to tackle three different kinds of cancer. Scientists at the University of Pennsylvania (UPenn), who are spearheading the small trial, hope to use the technique to edit genes in a patient’s own immune cells, reprogramming them to recognize and attack cancer at the first signs of growth.

In an eyebrow-raising twist, the trial is funded by former Facebook president Sean Parker. Earlier this year, Parker announced a $250 million foundation aimed at uniting immunotherapy researchers to “solve cancer.”

But it’s not yet all systems go. The proposal still has to pass the scrutiny of the FDA and the institution’s ethics boards. That said, the federal endorsement is a huge step towards actualizing the trial.

The news has taken the scientific community by storm. Although whispers of CRISPR use in humans have long circulated the field, the earliest clinical appearance for CRISPR was thought to be slated for 2017, in a trial for a rare type of blindness.
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