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There is clearly tumor lesion shrinkage, but falls short of a RECIST PR. Higher dose may get them there.
Based on experience with NY-ESO TCR therapy, the benefit of treatment may become evident at higher cell doses
BASEL, Switzerland, Oct. 09, 2018 (GLOBE NEWSWIRE) -- Axovant Sciences (NASDAQ:AXON), a gene therapy company developing innovative treatments for debilitating neurologic and neuromuscular diseases, today announced upcoming presentations regarding its investigational gene therapy programs, AXO-Lenti-PD and AXO-AAV-OPMD, at the Annual Congress of the European Society of Gene and Cell Therapy (ESGCT) being held in Lausanne, Switzerland from October 16th to 19th, 2018.
Prosavin®, a dopamine gene therapy for advanced Parkinson’s disease: 5 years phase I/II clinical update
Date: October 17, 2018
Time: 13:10-15:10 CEST
Location: Garden Floor, Poster session 1
Poster Number: P201
AXO-Lenti-PD for Parkinson’s disease: endogenous dopamine production by intraputamenal three-gene transfer
Presented by: Fraser Wright, Chief Technology Officer of Axovant
During the lunch workshop on the use of lentiviral vectors for in vivo gene therapy
Date: October 18, 2018
Time: 13:15-14:15 CEST
Location: Garden Floor, Conference room 2/3
Fraser (formerly Co Founder and Chief Technology Officer
Spark Therapeutics, Inc.)
Good news. Orchard should be quite a valuable company in time. OXB will do well.
Additionally, Oxford BioMedica will receive a low single-digit royalty on net sales of licensed products until January 31, 2039. In the event the products are used for compassionate use, these royalties are reduced by a mid-double-digit percentage. Orchard Therapeutics is also required to pay a set monthly fee to Oxford BioMedica in the event the Group's system for generating stable cell lines is used.
The last line may be a pointer to the earning power of TRiP ?
This is from the CF deal; The collaboration may also include an evaluation of Oxford BioMedica’s Transgene Repression in vector Production (TRiP) System, and the development of stable producer cell lines for large scale production of the lentiviral vector.
HTTps://www.oxfordbiomedica.co.uk/news-media/press-release/oxford-biomedica-uk-cystic-fibrosis-gene-therapy-consortium-boehringer
Oxford BioMedica currently owns 1,111,924 shares in Orchard Therapeutics
https://uk.advfn.com/stock-market/london/oxford-biomedica-OXB/share-news/Oxford-Biomedica-PLC-Details-of-alliance-with-Orch/78403980
Wet AMD
In a phase I clinical trial for wet AMD, a gene therapy called “Retinostat,” delivered by injection under the retina, has proven safe. It also continues to make proteins that inhibit abnormal blood vessel growth, called angiostatin and endostatin, for at least one year after injection. These proteins were measured in fluid samples taken from inside the eye. Future clinical trials will likely test whether Retinostat can block the growth of harmful blood vessels in patients with wet AMD and diabetic retinopathy.
hTTps://www.brightfocus.org/macular/article/gene-therapy-eye-disease
Stuart, finances for Axo-Lenti-PD pretty spectacular. Firmly believe accelerated route to market.
A couple of new assets will be moved into the pipeline over the next few months from the lab. OXB will talk about those soon. These match the direction of existing clients. Maybe brain (axovant) liver ( Sanofi ) etc. ?
Revenue potential looks fab. Substantial growth.
Hope to be a part of Novartis` drug progression beyond the 2nd CAR T.
Pipeline has never looked healthier in term of feasibility studies for new customers.
Enormous growth opportunities.
Mentioned process C
3 clean rooms working flat out. Bullish about 2nd half revenue.
TRiP improves by x 10 so looking at out-licensing deal of up front and royalty. Does lenti and AAV. Good IP too.
Working on an awful lot of feasibility so expect further deals over next 12 months.
Manufacturing process is difficult so a real barrier to entry for others.
Fast forward to 1:01:57 to listen to our interview with the #BBCRadioOxford, where Chief Technical Officer, James Miskin discusses Kymriah and the NHS’s approval to treat children and young people with a form of leukaemia hTTps://bbc.in/2oMr88E #genetherapy
Canadian approval now:
HTTPS://www.newswire.ca/news-releases/novartis-receives-health-canada-approval-of-its-car-t-cell-therapy-kymriah-tisagenlecleuceli-692581041.html
Novartis receives Health Canada approval of its CAR-T cell therapy, Kymriah™ (tisagenlecleucel)I
Health Canada has approved Kymriah for use in pediatric and young adult patients 3 to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) who are refractory, have relapsed after allogenic stem cell transplant (SCT) or are otherwise ineligible for SCT, or have experienced second or later relapse; and for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphomai.
hTTps://markets.businessinsider.com/news/stocks/novartis-receives-health-canada-approval-of-its-car-t-cell-therapy-kymriah-tisagenlecleucel-i-1027513253
hTTps://phss.co.uk/events/EventDetails.aspx?id=1038313
Lonza and Oxford Biomedica attending
spec calls for 80 percent of those cells to be viable That's more stringent than we even saw in the clinical study, quite a few patients in the 70s. But if you don’t have 80 percent of your cells viable at end of the manufacturing process, then it's “out of spec
https://www.bloomberg.com/news/articles/2018-08-30/a-year-after-cancer-milestone-novartis-s-barrett-talks-next-steps
If I can find these companies before mainstream investors or corporate acquirers, the upside is significant, making them great candidates for the core holdings bucket of the Fidelity UK Opportunities Fund .
https://www.fidelity.co.uk/markets-insights/viewpoints/world-leading-tech-stocks
Pharmaceutical research has always been an area of expertise in the UK, and occasionally I come across a company which offers the twin benefits of improving healthcare provision as well as giving shareholders a healthy glow. Oxford Biomedica , a company that through their unique LentiVector delivery platform allow gene therapies to be delivered safely to patients, a system that may revolutionise some areas of cancer treatments and degenerative diseases. This is a top 5 position at 3.3% of the fund.
Overlooked molecule might be key to how well cancer-fighting CAR-T cells work
By Sharon Begley @sxbegle August 21, 2018
The new findings add to emerging evidence in favor of 4-1BB over CD28 presented at this year’s annual meeting of the American Society of Clinical Oncology. There, scientists from the Beijing-based biotech startup ImmunoChina Pharmaceutical Co. reported results from a clinical trial of 47 patients with B-cell acute lymphoblastic leukemia. They received either CD28 CAR-Ts or 4-1BB CAR-Ts.
All 28 patients receiving 4-1BB CAR-Ts had an “objective response,” meaning fewer malignant cells after treatment; 15 of the 17 patients receiving CD28 CAR-Ts did. In addition, blood levels of CAR-Ts in the 4-1BB patients were “significantly higher” than in the CD28 patients, which might bode well for continued efficacy and therefore, for staying cancer-free longer. Almost all the patients (45) suffered cytokine release syndrome, but the five with the most severe form were in the CD28 group. The ImmunoChina scientists wrote, “4-1BB CAR-T cells show enhanced safety, efficacy, and expansion” compared to CD28 CAR-Ts, suggesting they would be a “superior therapeutic strategy.”
When Novartis began collaborating with the University of Pennsylvania to develop CAR-T therapy, Brogdon said, the academic scientists were testing both CD28 CAR-Ts and 4-1BB CAR-Ts in lab animals. “They observed enhanced persistence of CAR-Ts with the 4-1BB,” she said, and those eventually became Kymriah.
And less toxic. hTTps://www.statnews.com/2018/08/21/car-t-cancer-costimulatory-domain-molecule/
So many new posts!
hTTps://apply.iintegra.com/vacancy/preview?id=15234&jbid=1052
The VPR team will have two over-arching aims: [1] transition early commercially relevant research-level technologies into the Rrocess Research and Development group, and [2] work closely with the Vector Service Team in generating vector preparations for collaborators and pre-clinical studies.
We are seeking a highly motivated individual to join the VPR team. The successful candidate will be taking a lead in:
Testing new chromatography approaches in relation to lentiviral vector purification
Cross-group activities within Platform Research; transitioning novel technologies from concept/proof-of-principle into downstream purification paradigms
Vector preparations for collaborative studies
Early product feasibility studies for external clients
Other activities within the Research Department e.g. MAb/protein purification
Vasant Narasimhan, CEO, Novartis speaking about Kymriah;
Published 4 hours ago August 21, 2018
"Our mindset is for the long run, of a 5 yr journey to get this to a blockbuster enterprise and that’s our general aim. Our aspiration is that this might be a major a part of the Novartis portfolio.
We’re actually Kymriah as a five-year journey. That is a rare drugs and one-of-its-type accepted in kids and offers sufferers who don’t have any different choice of therapy. It’s a science to take the cells out of the physique and reprograming them is actually outstanding however it’s also so new that it’ll take time for the hospitals to be able to take this on and handle such a posh remedy.
From our facet, we have to scale up the operations. Total it’s in keeping with the expectations and we all the time knew that this will likely be a long run technique for cell remedy. The necessary factor is as we go international, and now we have introduced the addition of a producing website in France, we are going to construct the infrastructure that additionally hyperlinks us to all of those hospitals.
We’re specializing in three areas – one is to spend money on manufacturing and make it very environment friendly and scale up, second we’re increasing extra most cancers varieties and we’d consider overlaying all B-cell cancers. My hope as a doctor is to stay in a world the place no affected person ought to die from B-cell most cancers.
We imagine there’s a new science rising that may enable us to create new cell therapies with totally different targets that cell therapies can assault, which we hope can apply to areas like stable tumors and that might presumably be the following breakthrough. Our mindset is for the long run, of a 5 yr journey to get this to a blockbuster enterprise and that’s our general aim. Our aspiration is that this might be a major a part of the Novartis portfolio.
hTTps://newpaper24.com/vasant-narasimhan-ceo-novartis-technology-news-ettech-newpaper24/
hTTps://www.pressreader.com/india/the-economic-times/20180821/281887299156825
Cancer stem cells (also called cancer-initiating cells) are implicated in tumor initiation, maintenance, and recurrence, leading to the poor effect of standard chemotherapies and tumor recurrence [31]. 5T4 was reported as a potential marker of CSCs in NSCLC squamous cell carcinoma [15]. 5T4-targeting ADC MEDI0641 could effectively kill cancer stem cells and non-cancer stem cells, resulting in regression of tumors such as breast cancer, head and neck squamous cell carcinoma, etc
hTTps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934552/
CarT 5T4 OXB 302 may prove to be a valuable asset.
(AAV). These gene therapy vectors do not integrate in the genome of the host cell, thus telomerase only performs its telomere-reparative actions during a few cell divisions before the vector is diluted out.
( surely this is why Lenti for Haemophilia will win out )
hTTps://eurekalert.org/pub_releases/2018-08/cndi-gtv082018.php
0 4 0
Vasant Narasimhan, CEO, Novartis speaking about Kymriah;
Published 4 hours ago August 21, 2018
"Our mindset is for the long run, of a 5 yr journey to get this to a blockbuster enterprise and that’s our general aim. Our aspiration is that this might be a major a part of the Novartis portfolio.
We’re actually Kymriah as a five-year journey. That is a rare drugs and one-of-its-type accepted in kids and offers sufferers who don’t have any different choice of therapy. It’s a science to take the cells out of the physique and reprograming them is actually outstanding however it’s also so new that it’ll take time for the hospitals to be able to take this on and handle such a posh remedy.
From our facet, we have to scale up the operations. Total it’s in keeping with the expectations and we all the time knew that this will likely be a long run technique for cell remedy. The necessary factor is as we go international, and now we have introduced the addition of a producing website in France, we are going to construct the infrastructure that additionally hyperlinks us to all of those hospitals.
We’re specializing in three areas – one is to spend money on manufacturing and make it very environment friendly and scale up, second we’re increasing extra most cancers varieties and we’d consider overlaying all B-cell cancers. My hope as a doctor is to stay in a world the place no affected person ought to die from B-cell most cancers.
We imagine there’s a new science rising that may enable us to create new cell therapies with totally different targets that cell therapies can assault, which we hope can apply to areas like stable tumors and that might presumably be the following breakthrough. Our mindset is for the long run, of a 5 yr journey to get this to a blockbuster enterprise and that’s our general aim. Our aspiration is that this might be a major a part of the Novartis portfolio.
hTTps://newpaper24.com/vasant-narasimhan-ceo-novartis-technology-news-ettech-newpaper24/
hTTps://www.pressreader.com/india/the-economic-times/20180821/281887299156825
Hi George, I don`t really understand it however Novartis did the deal with Penn 2012 so hopefully they have the rights.
Best wishes, M
Notice of Interim Results
London, UK - 15 August 2018: Oxford BioMedica plc ("Oxford BioMedica" or "the Group") (LSE:OXB), a leading gene and cell therapy group, will be announcing its interim results for the six months ended 30 June 2018 on 13 September 2018.
A briefing for analysts will be held at 12:00pm GMT on 13 September 2018 at 85 Gresham Street, London, EC2R 7HE. There will be a simultaneous live conference call with Q&A and the presentation will be available on the Group's website at www.oxfordbiomedica.co.uk. An audio replay file will be made available shortly afterwards.
hTTps://seekingalpha.com/news/3375276-european-court-makes-restrictive-ruling-genome-editing?dr=1#email_link
European Court makes restrictive ruling on genome editing
The European Association for Bioindustries says the ruling contradicts a previous document that states precise gene editing technology (e.g., CRISPR/Cas9) may not need to be strictly regulated
Stephan Grupp, MD, PhD
Upfront Car T soon.
good news for French patients desperately awaiting CAR-T therapies in their homeland: ATUc (temporary approval) granted by ANSM in France for Yescarta & Kymriah in DLBCL (+ ALL for Kymriah) from the end of July to the end of the year
hTTp://ansm.sante.fr/S-informer/Actualite/Therapie-genique-acces-precoce-aux-premiers-medicaments-innovants-CAR-T-Cells-dans-le-traitement-de-certains-cancers-hematologiques-Point-d-information
HTTPS://edge.media-server.com/m6/p/bmeuzv3m
HTTP://investors.axovant.com/investors/events-and-presentations
They are intending to advance Prosavin also.
"We are working with Oxford Biomedica, the recognised world leader in gene therapy manufacture"
Expect to move it to earlier stage disease patients.
That Axovant team is very impressive.
http://www.ocquila.com/ Oxford Biomedica, "The unambiguous world leaders in Lentiviral manufacture." Axovant CEO quote.
SIX OXB team moving to Axovant for the programme.
Re the recent FDA comments, they will be looking for accelerated pathways to approval.
For Oxford Biomedica, the deal is evidence of new-found partnering interest in the company since the initial approval last year of Basel-based Novartis AG's CAR T therapy Kymriah (tisagenlecleucel) in B-cell acute lymphoblastic leukemia. Oxford, which produces lentiviral vector on behalf of Novartis, has gained a new-found prominence as a result and has received "quite a few approaches" from prospective partners, Dawson said. The company is now pursuing a hybrid model, offering its manufacturing and process development expertise to companies with their own gene therapy programs, while also developing proprietary programs of its own. At this point, it is looking to partner or spin these out before they enter the clinic. It is currently seeking venture capital funding for a new formed spin-out company, Ocquila Ltd., to take on two ocular disease programs, OXB-202 in development for corneal graft rejection, and the wet age-related macular degeneration (wet AMD) therapy OXB-101. A deal could be imminent. "I would be looking for some news flow or other this calendar year," Oxford CFO Stuart Paynter told BioWorld.
HTTP://www.ocquila.com/
Thanks George, I`ll share that. It`s looking very good for OXB
FT Buy OXB
https://www.thetimes.co.uk/article/biomedica-has-right-formula-for-growth-fxss7m8lx
It£s been a turbulent year for British biotech. Shield Therapeutics, Faron and ImmuPharma have all crashed on failed clinical trials £ leaving investors shouldering heavy losses.
Yet Oxford BioMedica (our business editor£s share tip of the year) is soaring. The cell and gene company£s stock has more than doubled this year, fuelled by lucrative deals it has signed with large drugmakers.
It inked a potential $842m (£623m) link with Axovant Sciences last week. The US start-up will license Oxford BioMedica£s early-stage treatment for Parkinson£s, which promises to halt progression of the disease. It paid a $30m upfront, including $5m pre-payment for manufacturing costs.
If Axovant is successful in commercialising the drug, conservative estimates put peak sales at £1bn. Oxford BioMedica stands to receive a royalty on every treatment.
The deal is a critical part of the strategy the company set out two years ago of spinning out or licensing its therapy pipeline rather than take on all the risk itself.
Oxford BioMedica is now worth £594.9m. However, the latest deal is not central to the company£s core valuation. Its key technology is a harmless virus (lentivector), which it uses to introduce DNA treatments into the cells of the patient and can be used in many therapy areas.
Its lentivectors are a key component of Kymriah, a new treatment for childhood leukaemia developed by Novartis. The drug has been approved and costs $475,000 per treatment. Oxford BioMedica earns a royalty from this medication, too.
The company made £37.6m in sales last year and is still loss-making. However, ebitda losses fell from £7.1m in 2016 to £1.9m last year. Moreover, the use of DNA to treat diseases is expected to grow into a $10bn sector with the company well-placed to take a share of this.
Oxford BioMedica raised £19.3m through an equity placing in March to expand its facilities. This will allow it to cut prices for its customers, and produce more of its lentivectors in one go £ increasing yield 10 times.
Biotech is not without its risks. Axovant£s share price plunged last September after an Alzheimer£s drug it bought from Glaxo Smith Kline failed in clinical trials. However, Oxford BioMedica£s strategy of spreading its risk and partnering with larger drug makers will stand it in good stead. The company£s stock is rising and is likely to climb further if more deals follow, as the company has promised. Biotech is risky, but £ as Oxford BioMedica is showing £ it can also come with great rewards. Buy.
The University of Pennsylvania has licensed technologies involved in these trials to Novartis.
CLL patient goes into remission thanks to single CAR T cell
Case study provides clues that could help improve response rates
Date:
May 30, 2018
Source:
University of Pennsylvania School of Medicine
Summary:
Researchers say a patient treated for chronic lymphocytic leukemia (CLL) in 2013 went into remission because of a single CAR T cell and the cells it produced as it multiplied, and has stayed cancer free in the five years since, with CAR T cells still present in his immune system.
has stayed cancer free in the five years since, with CAR T cells still present in his immune system. The findings, published today in Nature, show the response is tied to where the CAR gene inserted itself into the patient's T cell DNA, a key factor that may help improve response rates to the therapy.
The American Cancer Society estimates there will be about 21,000 new CLL cases in 2018
HTTPS://www.sciencedaily.com/releases/2018/05/180530133022.htm
PramBigear
29 May '18 - 21:17 - 196 of 205
0 9 0
AGM Report
Generally, as might be expected, there was a pretty happy and relaxed atmosphere. Certainly the ‘happiest’ I have encountered since the Trovax ‘deal days’.
The Chairman opened the meeting and allowed ‘general questions’.
This was the commonly expressed ‘Capital raising complaint’. This breaks down into”
- why do it” (“needed the funds to finance the Novartis deal”).
- “Why not give existing shareholders the same opportunities and rights” (We took advantage of market conditions at that time”).
During this exchange we learned that Oaktree Capital did get warrants and that they have not yet exercised them.
The questioner asked if individual shareholders could have similar opportunity to obtain warrants (“We note your request”).
The usual business of the AGM: Remuneration; re-appointment of directors; approval of auditors; and even the ‘special resolutions overriding the shareholder protection of the Companies Act (Giving the directors right to increase and authorise share capital, waive pre-emption rights, reduce notice of meetings to 14 days). All passed without debate or disapproval.
John Dawson Presentation.
Before my notes it is worth rehearsing the points posted by Marcus, from post #170, my comments from the meeting in brackets.
The Company estimates the lentiviral vector bioprocessing market was worth around $200m in 2017 and will grow to $800m in 2026
• Oxford BioMedica estimates it currently has ca. 15% of global market share that includes academia and industrial market participants
• Oxford BioMedica believes it can grow its market share to 25% to 30% with new facilities to be funded from proceeds of the placing (So $200m to $300m from manufacturing alone)
• Potential milestone and royalty receipts are in addition to these estimates which are for bioprocessing revenues (Royalties are higher for newer deals. For example royalties on Bioverativ are double those from Novartis. In fact although royalties are less than manufacturing profit at present this is expected to reverse as time progresses.)
Expect gross income to continue to grow strongly • 3 GMP suites and laboratories fully operational (“Lots of partners already and we expect a lot more”, Sanofi, Novartis, Bioverativ, Glaxo, etc. and they are meeting and progressing many more. The implication was that they can and are picking and choosing.
• Multiple revenue generating partners with potential for further new partnerships in 2018 (including expansion of business with GlxoSmithKline)
• Bioverativ $5 million license payment received as part of agreement
• Kymriah royalty income expected to grow strongly across the year (“including Novartis 2nd indication which OXB can’t tell you but look at Novartis report online and you can see what it is”)
OXB-102 Phase I/II clinical study to be initiated in H1 2018
• Partnering discussions ongoing for in-house priority development programmes (Impression given that there IS a partner in late stage discussion but to ensure he commits they are finalising the trial protocol and have agreed internally to take the phase ½ forward in the second half of this year if the partner doesn’t).
Some particularly interesting comments made during the above presentation:-
- “We are cash flow positive and can fund all operations to the end of 2019, including capex.”
- “Lots of people coming to see us since Kymriah approved”
- “We have a broad pattern of working with partners (excitedly…) we have learned a lot from discussions with partners and potential partners which we take back to the company.”
- They agree there are many competitors able to produce a lentivector, but none to the same quality and volume as OXB. OXB have to thank Novartis for their assistance and guidance in development of ‘quality systems’ (which few, if any can match).
- “ ‘CNS’ (sorry, I can’t figure what that is!), Lung and Liver all require huge volumes of Lenti by their nature. Few can do that. “
- “We are some years ahead of our competitors”
In particular Bioverativ will require huge amounts of Lenti for their project (I don’t understand why) and here is where our technology is ‘disruptive’.
• Using current manufacturing one dose would cost $4m to produce…. Impossible;
• Our 200ltr production improves this by a factor of 10…. Makes dose $400k still too high;
• But our TriP technology improves that by another factor of 10…. $40k!
The impression given is that no-one else can do that.
SPIN OUT projects
John recognised that “we tick all the boxes for Lenti, but we need a ‘Big Tick’ for this. It is coming!”
John had made a low key comment about spinning out Ophthalmology products, he said it hastily, and I may not have caught the right tone or facts. I think he said to a US partner….. However,…
Peter Nolan is retiring during the next year. He is key, and two people are replacing him over time. In a chat with him after the meeting he told me that although he was retiring, he expected to be busy for months to come as he was working on a partnering project with ophthalmic products? I wonder? A US company, or Sanofi? After all, the latter already have two of the products.
NEWFLOW
All 2nd half year.
Novartis 2nd Car-T indication;
Orchard to file their BLA;
Bioverativ clinical progress (worth $100m over 3 years to OXB, but don’t yet know the rate of progress);
More Lenti manufacturing deals (presumably to be executed 2019 as Novartis will take almost all current production);
Parkinson OXB 102 spin out;
Glaxo expansion of deals.
QUESTIONS
Capacity?
OK now to end 2019, new facility then comes on-line and doubles it.
Capital?
The $19.3m raised earlier is earmarked for the production expansion. “No need to raise cash for operations”.
Trovax?
“No longer working on it”.
Royalties?
“2014 painted a picture of royalties being a big thing. That is not true yet, but it will be.”
People?
Most of current spend is to meet manufacturing and royalty needs.
Hope I haven’t missed too much!
Pram
I think this is the start of the push for 1st line treatment. Kymriah has the advantage of freezing and out patient use. CRs out to 4yrs now in dlbcl
CAR T-Cell Therapy in DLBCL: Centers of Excellence
Panelists: Stephen J. Schuster, MD, University of Pennsylvania
Published: Friday, May 25, 2018
In the coming months, we also intend to further clarify our approach to the regulation of gene therapy. We’re going to provide a comprehensive framework that will include new guidance on manufacturing standards and approaches; as well as clinical guidance that lays out development pathways and potential accelerated approval endpoints for products that target specific disease areas like haemophilia.
We’ve reached an inflection point when it comes to gene therapy. The key enabling technology was the advent of more reliable vectors to deliver the target genes.
We’re now at a turning point where these treatments have the potential to become a backbone of modern medicine.
It’s similar to the inflection point when we first perfected the humanization of antibodies. It was a turning point in the use of antibodies as drugs. In a similar way, the advent of the lentiviral vector is an analogous product innovation that has opened up a huge clinical opportunity. Gene therapies using lentiviral and certain other vectors now hold out the promise of curative treatments for many vexing disorders.
Our obligation is to design a framework for the evaluation of these products that enables the efficient advance of these opportunities, while taking steps to ensure their safety.
When it comes to gene therapy, often the hard questions aren’t around efficacy. Many of these treatments look like they’ll be highly effective. Efficacy is often established early in the course of development, and in small series of patients.
The critical questions don’t necessarily turn on the clinical portion of the review, but on the product related issues.
These include the theoretical risks from off target effects, and on the durability of the response. They turn on complex issues associated with manufacturing and gene delivery.
A lot of the IP is also embedded in the manufacturing processes. And in some cases, we may be seeing product developers re-engineer these manufacturing processes in ways that may be geared less toward improving the products, and more toward circumventing some of the stacked royalties that exist in this field. Our job is to make sure these manufacturing changes don’t also introduce new risks. So we need to make sure we’re applying proper attention to all of these product-related regulatory issues.
In short, some of the hardest regulatory questions may turn less on the clinical evaluation of the technologies and more on the product specific and manufacturing issues that relate to the long run performance of these constructs.
This requires us to re-think our regulatory model when it comes to these products, to make sure we’re taking an efficient and science-based approach. Where the critical questions turn on long-term safety and durability, we need adequate policies to evaluate these products post approval.
For gene therapies that target serious conditions and offer potentially curative effects, the accelerated approval process may be ideally suited to allowing us to achieve a twin purpose – to expedite market entry while, at the same time, ensuring that we have strong post-market tools to continue to evaluate the safety of these product effects post approval.
Keynote Addresss by Commissioner Gottlieb to the 2018 FDLI Annual Conference
Speech by Scott Gottlieb, M.D.
Commissioner of Food and Drugs
Keynote Address at the 2018 Food and Drug Law Institute Annual Conference
Washington, DC
May 3, 2018
HTTPS://www.fda.gov/NewsEvents/Speeches/ucm606541.htm
In the long term we anticipate that OXB’s royalty revenue will outstrip its manufacturing revenue, particularly in indications/partnerships where OXB’s latest IP has been implemented.
In the long term, we forecast a growing multi-source royalty stream for OXB that will contribute alongside bioprocessing (manufacturing) revenue to its growing top line.
Due to the complexities of delivering gene therapies on this scale, we forecast that OXB is likely to receive a higher royalty rate than it receives from products that need smaller vector quantities, eg Kymriah in pALL or DLBCL.
We forecast that OXB sells vector batches to Bioverativ for $1.5m a batch, with peak gross margins of 30%.
We assume a larger than usual royalty rate of 7%. We believe OXB will likely have to incorporate an array of next-generation technology like TRiP to be able to reach the required manufacturing yields for these large indications, in turn driving increased royalties.
We forecast that OXB sells vector batches to Orchard for $1.5m a batch, with peak gross margins of 30% We assume a peak royalty rate of 2%
We forecast that OXB sells vector batches to Immune Design for $1.5m a batch, with peak gross margins of 30%. 2% royalty
http://www.edisoninvestmentresearch.com/research/report/oxford-biomedica73735/full
Findings from the study suggest that CTL019, despite absent on most neoplastic plasma cell population, has the ability to favorably alter the clinical disease trajectory in multiple myeloma patients.
HTTP://insights.bio/cell-and-gene-therapy-insights/2018/04/25/car-t-therapy-in-combination-with-standard-therapy-improves-duration-of-response-in-multiple-myeloma-patients/
OXB are doing a share consolidation of 50-1. Some are speculating that they may be considering listing in the USA.
Further to my #164, I note the following for NYSE -
"The New York Stock Exchange has two sets of listing standards for international companies: domestic standards and worldwide standards. Regardless of which standard is used, an international company must have a minimum share price of $4 at time of listing."
[From HTTPS://www.nyse.com/get-started/international/choosing-the-right-listing ]
NASDAQ appears to have a similar rule applied to a peiod of 90 days prior to listing.
This would clearly justify a 50:1 consolidation against my earlier suggestion of 20:1 being preferable or adequate.
The limit for AMEX is $2.00.
624 - The Use of Automation in the Development of Lentiviral Vector Producer Cell Lines
In conclusion, the isolation and screening of larger numbers of clones (>1000) using the ACSS leads to the selection of higher titre LV producing clones than previously achieved when screening smaller numbers of clones (100-200) manually. OXB now has capability of leveraging this technology in generating cell lines based on tet-repressor and/or TRiP system for serum-free, suspension production of viral vectors.
HTTPS://plan.core-apps.com/asgct2018/abstract/cbbcf41d-afe9-4b9a-a37e-2327363445f1
$GILD Yescarta Q1 sales $40M beat consensus of $16M (though buyside expectation higher after $NVS Kymriah number and WSJ story)
In April we announced an agreement to acquire AveXis, which gives us a platform now in gene therapy and builds out our neuroscience portfolio. So, as you can see, we continue to progress on this strategy and look for bolt-on opportunities in line with our capital allocation priorities.
Kymriah and DLBCL remains on track for U.S. approval in Q2 of this year as is Aimovig our first-in-class CGRP monoclonal antibody. We also filed ACZ885 for CV risk reduction in both U.S. and Europe, that filing was completed in December. And we're on track to complete our rolling submission of BAF312 in Secondary Progressive MS in Q2 and RTH258 in Q4 of this year. So, you can see taken together, 13 potential blockbuster launches assuming the closure of the AveXis transaction. So very strong profile that we believe can drive the growth for the next 5 years and beyond.
And of course, we have continued to expand our efforts in CAR-T cell therapies and related therapeutics and impact cancer care.
On the last topic, on the bispecific versus CAR-T therapy. I think the clinical thing here is durability. I mean we know that with Kymriah and pediatric ALL we seen durability of up to 5 years in many of the patients. In DLBCL, we're following where we know patients to get the 6-months usually stay in response up to 12 months and then longer term. I think the open question with bispecific and some of the other technologies as they can lead to durable response, because with these patients what you’re looking for, is a durable response to give them back their lives. So that’s going to be the open question. I don’t know the answer, but we do know that CAR-T cells because of the ability for the T-cell clones to expand again when the cancer recurs, when you do have patients that have at that long-term response they tend to stay in a positive state. So that’s how we think about the threat of bispecific and other technologies versus CAR-T cells.
We have the 13-potential blockbuster launches coming. We have a world-class R&D engine. Second, strong and growing dividend that does not change and third to use our capital defined strong bolt-ons that continue to build up our business in our core therapeutic areas and also bring new platforms like gene therapy or like radio nuclei therapy into the company or even digital therapeutics.
Second, we are a leader CAR-T, we have Kymriah we have a broad portfolio of CAR-Ts coming behind that. So, we have that as platform. We have immuno oncology, we have the 20 or so assets that are in the clinic evaluating them, but we'll take a stronger look at them. And then we brought in regular nuclide therapy, transformative in neuroendocrine tumors. We'll see how it unfolds in prostate cancer also looking at gastric cancers. So, we are strategically trying to take a broad position. So, we're not overexposed to IO per se. And it's not a binary event for us whether IO pans out for the company.
And the last one on priority review vouchers, you are correct we have multiple priority reviewed vouchers given the strength of our pipeline. We think it's prudent to have multiple priority review vouchers to enable us to accelerate programs. We'll comment on which priority vouchers we have used and which programs when we've received acceptance of the file from FDA and their confirmation on the priority review. So, you'll be hearing more from us over the course of this year.
Vasant Narasimhan
Great and on Kymriah.
Elizabeth Doherty
Yeah, sure. Love to give a little bit more color on that. As we've talked about before, their revenue in Q1 was actually in line with our expectations. We have been focused on exactly what you're talking about expanding the sites, we now have 35 sites up and running. Just keep in mind the new therapy is the new therapy for us it's also new therapy for the hospitals and centers. So, we spent a lot of time making sure that the experience that they're having is a positive one and that we are getting the logistics down properly. And we feel very good about where we are in preparation for the DLBCL hope for anticipation of expansion soon. So, I think we saw the reimbursement, we have not had any issues as reimbursement that's going very smoothly. The sites are up and running, we feel very good about that and in anticipation again of the expansion of the label soon. So, I think so far so good, yes, we expect that we'll see the trajectory improve overtime. But again, keeping in mind, not only with ALL but also with DLBCL outlook starts to launch that these patients need to be referred to the centers. And so, I think you'll see a continuous improvement quarter-over-quarter. But you will see it, it will take time for these centers to get up and running and used to use in this new therapy.
https://seekingalpha.com/article/4164209-novartis-ag-nvs-q1-2018-results-earnings-call-transcript?page=21