http://journals.lww.com/immunotherapy-journal/Abstract/publishahead/Preclinical_Assessment_of_CAR_T_Cell_Therapy.99504.aspx

The most high profile was the world's first gene therapy for cancer, Kymriah, developed by Swiss firm Novartis with British biotech Oxford BioMedica.

Novartis' Kymriah, approved in the US, is the first so-called CAR-T cell therapy for cancer, a one-time treatment that works by modifying a patient’s cells so they can spot and kill cancer cells.
HTTP://www.telegraph.co.uk/business/2017/12/12/gsk-hails-progress-advanced-cancer-drug/

HTTPS://seekingalpha.com/article/4131387-novartis-nvs-highlights-ash-sabcs-slideshow?auth_param=1d8lsm:1d309p1:93c5affae499caa3b388802d8be6d971&uprof=82&dr=1



DLBCL in FIRST RELAPSE

Pages 4 and 5 make good reading

the cocktail of chemotherapies they receive come with considerable side effects, with many survivors experiencing serious health conditions later in life as a result of the treatment.
For parents of children with leukemia who have failed conventional treatments already, the decision to try CAR T-cells is easy. For the first parents that consent to the inevitable chemotherapy-free CAR T-cell only trial, it will be a leap of faith. If all goes well, their children will be the first ever to survive leukemia without any chemotherapy treatment.

In May this year Emily, the first patient to get CAR T-cells celebrated the milestone of being five years cancer-free. Undoubtedly there are still numerous challenges to overcome before CAR T-cells become a mainstream therapy for multiple cancer types, but in five years from now, hundreds if not thousands of others will be joining Emily in this currently unique club.
HTTPS://www.forbes.com/sites/victoriaforster/2017/12/12/chemotherapy-free-cancer-treatments-move-closer-to-reality/#66245bcd6676

Forbes

Incoming CEO at Swiss drugmaker Novartis , Vas Narasimhan, said he isn’t interested in following the herd in drug development.

“How do you make smart contrarian bets?” Narasimhan said of his strategy for Novartis Wednesday at the Forbes Healthcare Summit in New York City. Narasimhan, who is the current chief medical officer and head of global drug development at Novartis, will take over for current CEO Joe Jimenez in February.

Novartis’ latest historic bet on cancer therapy Kymriah has made waves throughout the industry. Approved by the Food and Drug Administration in August for use on children with acute lymphoblastic leukemia, it is a novel therapy called a chimeric antigen receptor T-cell, or CAR-T that genetically modifies a patient’s own white blood cells, training them to essentially hunt down and kill tumors.



“We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer,” FDA Commissioner Scott Gottlieb said in a statement in August when Kymriah was approved. “New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses.”

While its implications are vast, the therapy does not come cheap. It’s list price is $475,000 per patient. “There’s no question that the list price raises eyebrows,” Narasimhan said. “We need to price our drugs at a cost-effective level that is acceptable for society,” he expanded. “[Value-based pricing model] is something we have to grapple with. We need to come up with different models for different medicines.”

FORBES reported in October that Novartis has said it's offering insurance companies a value-based pricing structure where it only pays for patients who enter remission within three months.

Johnny Wolf
Austin Schuetz, one of the first patients to benefit from Novartis' CAR-T treatment, on stage at the Forbes Healthcare Summit with Leukemia & Lymphoma Society president and CEO Louis DeGennaro.
One of the earliest beneficiaries of this therapy was 10-year-old Austin Schuetz. Shortly before his 3rd birthday he and his parents were given a devastating diagnosis, acute lymphoblastic lymphoma. Over the next few years of his treatment, which included chemotherapy, radiation and a bone marrow transplant, he continued to have relapses until his parents, Kimberly and Jeffrey Schuetz, learned of Novartis' phase one clinical trial for Kymriah. Austin was eligible and he enrolled soon after in 2013.

“We would just kind of wait in the wings, and hope was all we had,” Kimberly Schuetz said at the Summit. Today, Austin, who joined his parents on stage at the Summit, is healthy thanks to the therapy.

“That’s what made me want to join the industry and certainly what motivates me every day,” Narasimhan said. “If we can solve puzzles that biology gives us and change patients lives.”

It's already difficult meeting demand for the inactivated viral vectors necessary for gene therapy research, but it's only going to become more difficult following the FDA's approval of Yescarta and Kymriah. The typical CAR-T clinical trial is only enrolling dozens of patients, but the addressable market for commercial-stage CAR-Ts totals in the thousands of people in the U.S. alone.

And therein lies a problem for drugmakers. To guarantee the quantities necessary for commercializing CAR-Ts, they need to either outbid one another to secure supply from third parties or build their own in-house production.

For example, Novartis locked in all the supply it needs for Kymriah back in 2014, but Novartis had to agree to pay Oxford BioMedica royalties on Kymriah's commercial sales to get the deal done.

At bluebird bio, management's nervous enough about viral vector supply that it's investing in a two-pronged approach. It's acquiring a 125,000 square foot manufacturing facility to make some of the viral vectors it needs. Additionally, it recently agreed to multi-year deals with three viral-vector manufacturing partners: Brammer Bio, Novasep, and MilliporeSigma, a division of Merck KGaA. These investments aren't going to be cheap, but they should be able to provide the viral vectors necessary for bb2121 (its multiple myeloma CAR-T), Lenti-D (its cerebral adrenoleukodystrophy gene therapy), and LentiGlobin (its beta-thalassemia and sickle cell disease gene therapy).

HTTPS://www.fool.com/investing/2017/11/30/are-viruses-a-problem-for-car-t-drugmakers.aspx

As the CAR-T pioneers know only too well, working with patient cells in creating a personalized therapy is no easy task. In gene therapy you have to extract the cells, include a viral vector and corrective gene and get it back into the veins of patients in a matter of weeks. Any interruption along that process — or loss of quality — can be fatal for a gene therapy company like bluebird. And manufacturing issues in general remain one of the most significant threats to any biotech looking to take breakthrough products into the market, as the FDA has highlighted time and again in recent years.

Given the stakes, and the complexity, I asked Adams what keeps him up at night.

“The thing that keeps me up at night,” says Adams, “is that the overall supply chain for gene therapy products is so complex” it can be hard to make sure all the pieces are under control.

“I suspect that Derek is sleeping a little better now that we closed the deal,” says Walsh.

HTTPS://endpts.com/bluebird-bio-orchestrates-a-series-of-deals-and-a-buyout-to-guarantee-gene-therapy-manufacturing/
marcusl230 Nov '17 - 12:05 - 27708 of 27726 2 0 Edit
"This is really an important time in gene therapy," says Dr. David Williams, professor of pediatrics at Harvard Medical School and chief scientific officer at Boston Children's Hospital

HTTPS://www.npr.org/sections/health-shots/2017/11/29/565728869/gene-therapy-shows-promise-for-a-growing-list-of-diseases

OXB just need to cling to Novartis` coat tails as

Penn are currently trialing CAR T in;

Lung Adenocarcinoma
Prostate
Ovarian Cancer
Multiple Myeloma
Peritoneal Carcinoma Pancreatic
Fallopian Tube Cancer
Non-Hodgkins Lymphoma (NHL)
Mesotheliomas
Pleural Malignant Melanoma
Breast Cancer
CD19+ Diffuse Large B-cell Lymphomas
Follicular Lymphomas
Mantle Cell Lymphomas
Mesothelioma Peritoneum

CART-PSMA-TGFßRDN Cells for Castrate-Resistant Prostate Cancer
University of Pennsylvania

HTTPS://clinicaltrials.gov/ct2/show/NCT03089203?term=car+t&lead=University+of+Pennsylvania&spons=University+of+Pennsylvania&cntry1=NA%3AUS&cntry2=EU%3AGB&phase=0124&draw=1&rank=4

CART-BCMA Cells for Multiple Myeloma

HTTPS://clinicaltrials.gov/ct2/show/NCT02546167?term=car+t&lead=University+of+Pennsylvania&spons=University+of+Pennsylvania&cntry1=NA%3AUS&cntry2=EU%3AGB&phase=0124&draw=2&rank=10

CAR T Cell Immunotherapy for Pancreatic Cancer

HTTPS://clinicaltrials.gov/ct2/show/NCT03323944?term=car+t&lead=University+of+Pennsylvania&spons=University+of+Pennsylvania&cntry1=NA%3AUS&cntry2=EU%3AGB&phase=0124&draw=1&rank=13

CAR T Cells in Mesothelin Expressing Cancers

HTTPS://clinicaltrials.gov/ct2/show/NCT03054298?term=car+t&lead=University+of+Pennsylvania&spons=University+of+Pennsylvania&cntry1=NA%3AUS&cntry2=EU%3AGB&phase=0124&draw=1&rank=16

Non-Hodgkins Lymphoma (NHL)

HTTPS://clinicaltrials.gov/ct2/show/NCT02030834?term=car+t&lead=University+of+Pennsylvania&spons=University+of+Pennsylvania&cntry1=NA%3AUS&cntry2=EU%3AGB&phase=0124&draw=1&rank=14

Malignant Melanoma
Breast Cancer
HTTPS://clinicaltrials.gov/ct2/show/NCT03060356?term=car+t&lead=University+of+Pennsylvania&spons=University+of+Pennsylvania&cntry1=NA%3AUS&cntry2=EU%3AGB&phase=0124&draw=1&rank=22


CD19+ Diffuse Large B-cell Lymphomas
Follicular Lymphomas
Mantle Cell Lymphomas

HTTPS://clinicaltrials.gov/ct2/show/NCT02650999?term=car+t&lead=University+of+Pennsylvania&spons=University+of+Pennsylvania&cntry1=NA%3AUS&cntry2=EU%3AGB&phase=0124&draw=1&rank=27

HTTPS://www.nytimes.com/2017/11/27/health/gene-therapy-virus-shortage.html
marcusl227 Nov '17 - 19:17 - 27668 of 27668 0 0 Edit
HTTPS://www.bbc.co.uk/iplayer/episode/b09gsf7v/bbc-news-at-six-27112017

BBC i Player, 6pm news, 1810, Oxford Biomedica and JD

Very positive day

Biggest thing for me was the trial starting soon (after FDA approval) for CAR T to be used as first line treatment instead of chemo etc. That will really expand the market for us. Cost will come down Doc before you start!

Using both cd19 and BCMA CARS 100% response

patient treated with Car T for prostate cancer

CD33 for AML starting at Penn 2018

Then JD expecting near capacity manuf. and further contracts.

page 8
https://seekingalpha.com/article/4124709-novartis-nvs-r-and-d-investor-presentation-slideshow?auth_param=1d8lsm:1d0mcpk:ca545c39dccbdbfde5f6ac49ff8aa9ca&uprof=82&dr=1

Novartis submits application to FDA for KymriahTM (tisagenlecleucel) in adult patients with r/r DLBCL, seeking second indication for first-ever FDA approved CAR-T therapy

https://www.novartis.com/news/media-releases/novartis-submits-application-fda-kymriahtm-tisagenlecleucel-adult-patients-rr

Ibrutinib plus CTL 019 CAR T, deep remmisions in patients with ADVANCED CLL, no hospitalisation for Cytokline release syndrome.

Carl June very excited, saying may be curative and and an out patient therapy !

Carl June thinks cancer vaccines with PD-1 may work;

HIV controlled with improved CAR T therapy; human testing planned next spring.

The improved therapy is planned for testing in a few patients beginning in the late spring of 2018, Riley said. It benefits from the work of scientists including University of Pennsylvania researcher Carl June, whose research led to the leukemia treatment, Kymriah, he said.

“It was really a very thorough investigation, and very timely,” Johnston said. “It looked at a lot of the critical components of how we’re going to apply CAR T cell therapy in HIV.”

HTTP://www.sandiegouniontribune.com/business/biotech/sd-me-immune-hiv-20171012-story.html

CTL019 has robust activity in DLBCL and triple-refractory Follicular Lymphoma and promising efficacy in Myeloma.

Carl June has achieved a complete remission in Multiple Myeloma !

The start of Kymriah expanding. I think that it will be a big earner eventually.

HTTPS://asia.nikkei.com/Business/Companies/Novartis-seeks-outcomes-based-pricing-in-Japan-for-cancer-drug

"The time has come to rethink Japan's drug-pricing system," said Ataru Igarashi, associate professor at the University of Tokyo's Graduate School of Pharmaceutical Sciences.

Novartis looks to apply in the first half of 2018 to have national insurance pay for Kymriah. Many drugs treating rare diseases take between seven and nine months to receive approval from the health ministry and are priced two months after that. The final price will likely depend on whether Novartis can apply outcomes-based pricing. If all goes smoothly, Kymriah could hit the Japanese market as early as next year.

Broker Forecast - Peel Hunt issues a broker note on Oxford BioMedica PLC
19 September 2017 | 08:40am
StockMarketWire.com - Peel Hunt today initiates coverage of Oxford BioMedica PLC [LON:OXB] with a buy investment rating and price target of 13p.


HTTPS://www.bioindustry.org/news-listing/ceo-update-monday-18th-september.html

http://www.bioworld.com/content/novartis-car-ts-kymriah-market-race-next-gen-winners-moves-high-gear-0

https://www.cbsnews.com/news/fda-approves-first-gene-therapy-in-u-s-to-treat-leukemia/

http://myfox28columbus.com/good-day-columbus/local-doctor-on-how-car-t-cell-therapy-will-help-in-the-fight-against-cancer

The treatment, Kymriah, developed with British Aim-listed biotech Oxford BioMedica, is a one-time 'CAR-T' treatment that works by reprogramming white blood cells to kill cancer, in this first case a type of leukemia.

http://www.telegraph.co.uk/business/2017/09/04/novartis-follows-cancer-breakthrough-new-ceo/

http://whyy.org/cms/radiotimes/

https://www.streetwisereports.com/pub/na/small-cap-biotech-benefits-from-first-fda-approval-of-car-t-therapy

CAR T 5T4

As previously reported, BTIG upgraded Juno Therapeutics to Neutral from Sell. Analyst Dane Leone said Gilead's (GILD) acquisition of Kite Pharma (KITE) will raise valuations across the CAR T space due to a scarcity effect of remaining players.

How do you turn world-leading British science into medicines?
TELEGRAPH

Both the Government and industry will be hoping to replicate the UK’s early wins in gene therapy, a field now boasting 60 firms with £1bn investment behind them. Among them is Oxford BioMedica, a company that has developed a novel lentiviral delivery mechanism for modifying genes.

The AIM-listed firm’s market value has jumped by almost three quarters since June thanks to its partnership with Swiss conglomerate Novartis, which got provisional approval for a landmark gene therapy for leukaemia. All of Oxford BioMedica’s operations remain in Oxford.

“We have looked extensively at other countries,” John Dawson, its chief executive, says. “But we are happy with what we’ve got. We’ve had a very good run of being supported by government.” That support has included millions of pounds of research grants.

Keith Thompson, chief executive of the Cell & Gene Therapy Catapult, the Government body behind the Stevenage facility, says: “We’re hoping that when companies grow out of using the facility and need a bigger place, they’ll simply build it down the road.”

HTTP://www.telegraph.co.uk/business/2017/08/26/do-turn-world-leading-british-science-medicines/

http://www.dailymail.co.uk/wires/reuters/article-4816352/Profit-finally-sight-gene-therapy-specialist-Oxford-Bio.html

http://www.oxfordbiomedica.co.uk/system/files/webcasts-and-audios/interimresults2017.mp3

CTL019 and other undisclosed CART products; over $100 million revenue potential over three years including $10 million upfront payment

The Group's priority in-house product development programmes continue to be prepared for clinical studies whilst discussions continue with potential partners
provides the Group with the financial flexibility to progress our key in-house programmes whilst continuing discussions with suitable collaborators

Next generation bioprocessing
The Group has recently developed a step-change in lentiviral vector production technology, moving from the use of labour intensive, manual, open processing in cell factories to next generation processing in single-use bioreactors. This new 200 litre process allows for larger scale production in closed single use systems, and has the potential to significantly increase capacity and efficiency. This increased efficiency will result in delivery of vector at lower cost of goods, which is important to support product commercialisation. The greater vector volumes that this process is capable of making also has the effect of unlocking indications that require large doses, such as muscle, liver and lung diseases. The Group has already successfully run the process at commercial scale.

technology companies Stratophase and Synthace, to further develop Oxford BioMedica's next generation suspension bioprocessing system. The two-year £2 million collaboration is partially funded by a grant from the UK's innovation agency, Innovate UK. During the collaboration, the partners will apply novel technologies to dynamically control bioreactors in real time and execute workflows to optimise operations and increase productivity.

Consequently, the TRiP system offers significant licensing opportunities for the Group as demand for vectors increases with the introduction of gene and cell therapy products.

OXB-102 (for Parkinson's disease), OXB-202 (for corneal graft rejection) and OXB-302 (for cancer)

OXB-102 (for Parkinson's disease)prepare the clinical study centres in Cambridge, London and Paris for initiation of the study. As a result, treatment of patients could begin early in 2018. In parallel a variety of potential financial partnership arrangements are being explored for each of the priority programmes. The Board is determined to ensure that the Group, and therefore shareholders, retains an appropriate share in the upside potential of these programmes. As such, the Group will continue to invest modestly in the programmes to maintain their momentum and to continue to enhance their value.

This has attracted additional interest from a range of potential partners and, as a result, the Group is conducting feasibility studies and discussions with a number of companies. The Group anticipates establishing further relationships over the next twelve months.

The Group intends to expand its portfolio of collaborations, and to attract third-party investment to accelerate the clinical development of its wholly-owned proprietary products.

HTTPS://www.pennmedicine.org/cancer/navigating-cancer-care/treatment-types/immunotherapy

HTTPS://www.iqmediacorp.com/ClipPlayer/?ClipID=8a5d3075-ce25-4607-a9ef-c4bc1b68eac3&ps=2

HTTPS://www.iqmediacorp.com/ClipPlayer/?ClipID=83288ed8-6b13-4835-a1ef-bece538512be&ps=2

HTTPS://www.iqmediacorp.com/ClipPlayer/?ClipID=bcaa22eb-2e5f-4f03-82a6-775aa148a31e&ps=2

Today's Independent:
HTTP://www.independent.co.uk/life-style/health-and-families/a-revolutionary-leukaemia-treatment-could-soon-be-approved-here-s-what-it-means-for-patients-a7883896.html

Two CAR T-cell therapy products, in fact, are currently being reviewed by the FDA
HTTPS://www.cancer.gov/news-events/cancer-currents-blog/2017/first-in-human-nci-immunotherapy

“The study validates genes we knew [were necessary] for tumors to respond to immunotherapy and turns up a number of unexpected, potentially interesting genes.”
HTTP://www.the-scientist.com/?articles.view/articleNo/50028/title/The-Cancer-Genes-Needed-for-Immunotherapy-Response/

http://time.com/4895010/cancers-newest-miracle-cure/?utm_source=time.com&utm_medium=email&utm_campaign=the-brief&utm_content=2017081212pm&xid=newsletter-brief

This will hopefully lead to improved manufacturing;

HTTPS://www.stratophase.com/

London, UK - 07 August 2017: Oxford BioMedica plc ("Oxford BioMedica" or "the Group") (LSE:OXB), a leading gene and cell therapy group, today announces that it has been granted a Manufacturer/Importer License (MIA), from the UK Medicines and Healthcare products Regulatory Agency ("MHRA"), to manufacture and distribute lentiviral vector material for commercial supply. This is in addition to the existing MIA (IMP) licence for Investigational Medicinal Products (IMPs) manufacture, which the Group has held for over 10 years.

http://www.oxfordbiomedica.co.uk/news-media/press-release/oxford-biomedica-announces-mhra-licence-commercial-supply

Immune Design's results appear to be very promising ;

HTTPS://seekingalpha.com/article/4094058-immune-designs-imdz-ceo-carlos-paya-q2-2017-results-earnings-call-transcript?page=2


03-Aug-17 08:46:43 8.60 18,428,995 Buy* 8.558.58 £ 1.585 M O

Oxford BioMedica Expands Collaboration, Inks Deal With Immune Design
Mon, 7th Mar 2016 09:25

"It's rare to hear regulators refer to the data as 'the most exciting thing I've seen in my lifetime.' I feel exactly the same way," said Maus. Upon learning about the decision, Maus said, "our whole lab was skipping and almost in tears at the same time."
HTTPS://www.aaas.org/news/personalized-precision-immunotherapy-tested-brain-tumors

"I am firmly convinced that CAR T cells and other immunotherapies have a chance to be a major breakthrough for glioblastoma," said Donald O'Rourke, a professor of neurosurgery at the University of Pennsylvania Perelman School of Medicine and first author on the paper.
"We were all taught for decades that the brain is an 'immunoprivileged' site and that immunotherapy would not work in the brain," said O'Rourke. "That is clearly old dogma that is not accurate."

Yes I listened to the meeting live, very emotional testimonies from the Parents of children saved by CTL019 and one for whom it came too late. Novartis and Miskin from OXB were very impressive.