Feb 2017 SB525 more potent than competing products from $ONCE and $BMRN
We haven't been a good partner. I understand what large pharmas want and we will be a good partner going forward.
April 2017 ARM Measuring off-targets is critical. You can what is misleading using bioinformatics to project or do what we do which is to use new sequencing technology to look at where you actually did cut to measure what happened.
Announcement May 10 that Pfizer signed collaboration agreement
Feb/Mar 2017 Oncology development at least as good as anyone else. Partner preferred due to company focus. Tech is so good could imagine spinning out as a separate entity.
Hemophilia B Genome Editing Trial is core of company. In vivo genome editing of albumin: "If this works..any gene into liver"
Apr 2017 Shire collaboration for Huntingtons: Science is the coolest he has seen since joining company. May 2017 cc: our expertise in gene regulation using Zinc Finger Protein Transcription Factor Technology will continue to expand
May 2017 Gene Editing Platform: Zinc Fingers continues to outpact the genome editing field. 60% of targets within 10 days.
May 2017 Lots of interest in Tauopathies-added to pipeline
Clear we had brilliant discovery scientists that needed to be paired with clinical dev/medical affairs.
Pfizer deal is biggest gene therapy deal ever signed.
Regulators on both sides of Atlantic have blessed approach in clinical trials.
Expect to see us partner Alzheimer's, CNS, Oncology work.
Gene editing is cutting edge so pushed forward on gene therapy which is what led to Pfizer interest in collaboration
Fabry working with experts in the field who all are in agreement with approach. Have Gene Editing approach in addition to Gene Therapy approach for Fabry.
Got involved with Tau because felt they had an advantage. Referenced quote: Brad Hymen see 1) (Mass General): "This is the best thing since sliced bread" his favorite way to control Tau. Currently in process to partner this. Lots of interested companies.
Very specific for Tau mRNA. Only 1 gene out of 26,491 impacted. New AAVs developing can go intravenous in a mouse and show effect of Tau in the brain.
Working on intermodule linkers (DNA links) which end up with much greater ability to design around target. 10 days = 60% of genome. Not only hit but have options to minimize offtargets.
In coming year: Number of data points. Lots of pipeline progress. This is best gene editing technology now we have to work out how to apply that. CNS and Tau deals to truly reflect a partnership with SGMO tech and others biology and translational methods. Also a solution for Oncology where SGMO do 80-90% editing to lead to excellent allogeneic Tcells
Our platform creates more opportunities that we are able to take forward ourselves. To maximize the value of this platform and to spread the use of the technology, we believe that externalization of R&D must be a central part of our strategy.
We are evaluating opportunities to pair our T-cell editing capabilities with the right oncology partner. Ideally, one with a strong library of targeting for immuno oncology applications.
We also expect eventually to enter partnerships to advance our gene regulation technology for CNS indications including ZFP mediated tau lowering for Alzheimer’s disease and other Tauopathies. We are also receiving inbound interest from many other companies who are beginning to evaluated genome editing as a novel solution for other diseases in different tissue types and therapeutic areas
Similarly with our middle pipeline, I am very pleased to report progress towards INDs and 2018 clinical trial starts. Next year, these will be our newest clinical programs and with Sangamo’s robust R&D engine, we have programs that will advance from discovery into preclinical research in preparation for INDs. There is such tremendous value in Sangamo’s platform which is a potential to deliver new assets for movement through early research and into the clinic.
Aug 15 2017 Wedbush PacGrow
Gone from 2 people to 25 people in clinicals. (Hire Ed Connors)
Platform> Didn't realize just how good the platform is.
Key will be right delivery.
We do editing/therapy in liver because that's what we can currently do. We are on the cusp of putting things in the brain and then control genes with transcription. Dream is to edit disease where it is through genome engineering.
Internally focus on Gene Therapy and the liver and to partner where cost of clinic, expertise is specific and a lot of competition. Will look at each area and decision when is optimal time to partner. Each project will be different. Some will be early when they have monkey data. Some will be after going into clinic. It will depend upon the value inflection point determined for each project.
Watch for our progress in LPN and AAV's. Love to be able to say they will be the company to solve delivery but they will be the company to understand deliver and partner to make it happen.
Ability to edit T cells is 2nd to none. No one else can do this. Pfizer deal brought this to the attention of others with a lot of incoming bus dev interest. A lot of activity currently and hope to partner going forward.
Hemophilia A currently have 2 sites open. Have 2 patients qualified for enrollment. Will press release when first is dosed. Expect all 3 will be successful (BMRN, ONCE) but pleased to have Pfizer when the go to commercial and reimbursement
Fabrys is a sleeper and they have beautiful data in mice. IND plan for next year and to move quickly into clinical.
3,000 zinc fingers library to go after the 60% of genome in 10 days.
Efficiency: Ability to edit by target. 80-90% efficacy. Focus on intended target at clinical scale.
Specificity: for any 20 base pairs they can land 450 zinc fingers. Contrast to other technology that is very restricted.
On target vs off target. With 450 zinc fingers, some will be eliminated so the optimization of on target and elimination of off target to be almost eliminated.
The challenge for the first ever in-human gene editing trial is with the delivery to the body.
the easiest place to deliver your gene or genome editing is to the liver, using AAV which are viruses that seek out and go to the liver cells
Zinc Fingers in the age of CRISPR? Sandy says that the older technology is much better developed for medical applications and is safer. The company has been able to get their off target effects to below the level of detection
When I was doing my postdoc, I would have used CRISPR. It’s better if you’re just wanting an easy experiment that isn’t about making a medicine but just getting a quick answer
Wedbush PacGrow Zinc Fingers, and that is, you know, some of the most beautiful molecular biology that I’ve ever seen, you can also do gene therapy, you can do cell therapy. Our experience with HIV means that we can do a range of T-Cell modifications that allows us opportunity, and to choose between the appropriate technology for the problem.
I’m going to show you some data that I think is a new way to look at it and why I think our platform is the way that gene editing will happen in the future
if you look at the pipeline we have, I hope you see that there is much more value than is currently appreciated
we have 4 things in clinical trials. We have a middle pipeline that I will touch on later of thalassemia, sickle disease, Fabry disease. And we have an earlier pipeline before that of oncology, CNS, and partnered with Shire we have the Huntington’s program
We do Genome editing vs Gene Editing: We make a cut and a new gene into the space. Not actually correcting a defect in gene. Putting a new copy of the gene in a safe space in the liver. We believe it's (zinc fingers) a better technology. CRISPR is very limited. We can do it with greater efficiency with less off-targets . Treating patients is different than a test tube. What we are doing is not a lab experiment...it will eventually become a medicine
We can target a cleavage event to any chosen base pair in the genome or, in not there, the immediate base pair next to it. CRISPR is one site in every 10-30 base pairs. Economic burden of hemophilia patients. We'll be costing society between $200k to $400k per year. Their medical bill today is $3m per year. (19 min mark)
What will make the biggest difference in the field is not the editing but the delivery. Today delivery is focused on Liver and Eye. Very soon there will be other ways to deliver. One is the brain. Most important is to deliver intravenously
Sangamo scientists have developed expertise across a range of genomic therapeutic areas, including gene therapy, gene regulation and cell therapy, in addition to genome editing. With our technology, we also see opportunities to treat diseases such as sickle cell disease and beta thalassemia through gene edited stem cells. There is great potential for neurodegenerative diseases as well. In Huntington’s disease, for example, we can use zinc finger protein transcription factors to specifically downregulate the longer, mutant huntingtin gene allele responsible for causing the disease, while leaving the normal functioning copy of huntingtin untouched.
Sangamo scientists published the first high-efficiency TAL nuclease (TALEN) architecture, which remains in use across the field. Due to clinical advantages in specificity and greater targeting flexibility, Sangamo chose to focus therapeutic programs on zinc finger proteins
We are focused on indications with a few hundred to a few thousand patients. For indications with greater numbers of patients, where large trials and significant investment are required, we will partner with the right companies
What will allow the field of genomic medicine to truly take off, however, is innovation around delivery. At the moment, we all use AAVs with strong tropism to certain organs, for example the liver. Resolving specific delivery mechanisms to other tissues will open other diseases to gene editing. We are on the cusp of having new vectors that can take us into the CNS, so companies such as Sangamo that can modulate expression of tau protein, for example. Cystic fibrosis is another disease amenable to gene editing, but what remains to be solved is delivery to the lung, past the mucus, and then to stem cells. The focus now is on delivery – how you can get your editing technology to the right tissue. The moment we can deliver our zinc finger proteins to tissues beyond the liver, the therapeutic potential of genome editing opens up dramatically. We are working on novel AAV serotypes and also on lipid nanoparticles that can potentially improve safety profiles and enable repeat dosing.
Curious if it's possible to connect the dots on collaboration timing. SandyM has been pretty vocal about wanting to sign external collaboration agreements where the target audience is large (ie expensive clinical trials) and where expertise is beneficial (oncology, CNS, etc). The industry events that Sangamo presents at are natural venues for discussion and to accelerate discussions.
April 27th presented at ARM Annual Cell Therapy Day in Boston
May 10-13 presentations at ASGCT
May 10 AH announced Pfizer deal
Since then Sangamo has presented at:
Wedbush Conference Aug 15th
Baird Conference Sept 6 NYC
Wells Fargo Conference Sept 7 Boston
Clearly no way of knowing when or if a deal will be announced. But the ability to communicate repetitively about their intent and to communicate with numerous parties at these conferences isn't insignificant. JPM conference early in the year is known as an M&A incubator because so much news is broken there and everyone goes with a potential dance card scheduling meetings after presentations. I wouldn't be surprised to see something announced next week. It's possible potential partners are waiting for some data from clinical trials but like Pfizer said, they became more interested after they heard about zinc finger gene therapy progress. Progress on Tau etc could be enough to push someone to want to strike a deal before competitors beat them to it.
Cantor Fitzgerald Sep 27
100 patients in HIV trials happily moving through the world with T-cells that have been edited.
They key to the future of Gene Therapy and Gene editing is the vectors to reach the correct tissues. Right now AAV viral vectors are the go to for delivery, but it is limited to brain, eye and liver. We need new vectors that can go beyond that. The company that conquers the vector of delivery will conquer the wold in genetics. Sandy referenced work in their lab to fix Cystic Fibrosis or DMD, but had no vectors to deliver it.
Partnering is logical thing to to. Done pfizer, shire and Bioveratis. There will be more of these.
10 min ZFN 2.0 not discussed here but per below slide, mentioned. Will come back and talk about. Each stage of Gene Editing optimized like a pharma company and have follow on molecules that improve 5, 10, 50 fold to current approach. If we can edit with current approach will have a pipeline of better things to come.
Still believe we will do an oncology deal. CNS/Tau really interesting data. Deciding how much data is needed to maximize value.
Imminently will hear of a patient screening MPS
Many approaches to treating beta thalassemia SCD but believe their specificity is better. Moving ahead very well. IND to be announced imminently
Cell therapy products slid shows 91% targeted insertion and 93% double KO. Stated latest results show 99% HLA/TCR knockout. PD-2 patented "i hope"
Ideal partner for a CAR-T company (partner)
Focus on Precision/Efficiency/Specificity for ZFN vs alternative approaches Cas-9.
ZFN 455 per 20 base pairs = thousands of architectures. HiFi Cas9 for CRISPR but only 1.1 per 20 base pair. Leads to 80-90% on-target with no significant off-target modification seen.
Look for new partnerships when discussing 2017 priorities at end of presentation.
Jefferies conference. What is clinically meaningful?
Often asked how will we know if that works. Three things we ought to think about whether it's worked. 1) Has editing taken place. We can do that in liver biopsies. Where we look to see has the enzyme been repaired into the Genome, and even that will be a momentous moment for all of us. Cause many of us in the field have been looking for gene and genome editing for many years. We're waiting for the moment when we first do it in humans. To do it in T Cells or outside the body was the first stage. Now to be able to do it, actually do it in vivo will be a great moment.
Those 2 trials are currently open in several centers in the US. They are actually recruiting, actively screening and we hope to be able to tell you about the first patient soon. But to the first stage will be has the editing taken place. This is a moment of history for the field.
The second question you will be able to look at. Can we measure the enzyme that is being produced from the liver. And because enzyme replacement only gives up very short term bolus, after the bolus is stated you'll be able to measure the enzyme.
The third question is. Is the patient better for it. Because for all the enzyme replacements used there is not a great understanding of the correlation between enzyme levels and effect. For very sensible patient focused reasons we started in adults rather than in children. And in adults many of the effects of the disease have already happened. Their stature is already determined, they are in a wheelchair or not. Their organs are impacted already. So the chance of these patients having a dramatic physiological effect is very low. But it allows us to show that editing works and the enzyme is present. Then we will work with the agencies to move into children where if we can get in before the effects happen we hope to have a significant impact on the lives of patients.
Jefferies London Nov 15th SandyM: - We were first to do gene editing: in cell, ex vivo and now in vivo - HIV: We have some new data that I think is quite exciting, that you'll hear about in the coming months. - Agencies in Europe have been very keen to have Sangamo go into pediatric treatment in clinic
Sangamo was first to do editing in cells, first invitro editing and now first in vivo editing.
In partnering meetings we mention we have filed to do 22 INDs
In rare diseases you can only move into clinic if patient and disease community support you. Naturally everyone wanted someone else to be "first" for in vivo which did delay a little. Normally you don't know the patient being dosed but this patient was so passionate he wanted to be interviewed and knows he is likely helping others more than himself.
Look at HIV trial, first to invitro editing. 102 patients have modified cc5 receptors, healthy and tcells remain edited with functional change. Goal was take them off antiviral agents but didn't understand the biology well enough. Lesson for all gene editing companies: Use tech to address understood biology. Shouldn't add a biology Q to a technology Q. As you look at these patients we've noticed the vital count within the tcell has dropped substantially, showing the editing function works and is still in effect with patients. Others are interested in taking this forward.
Q: What is your approach to opportunities now vs past? A: Great Q discussed just last night. Medical need is first requiring a patient population with significant condition for which this is the solution. We do something to their DNA which puts the need first. But as a bus, we have to consider shareholder value by looking at size of patient population. With technology they can target any nucleotide in genome to focus on every possible disease. Leads to some ultra rare opportunities that they can partner with others interested in pursuing. Leads to question of commercial vs platform company. They believe they can and should be both. Platform is too good to solely use it for their own commercialization efforts.
Fantastic T Cell editing capability internally came from HIV and now applied to CAR-T. Repeated the efficiency statement of 99.5% for 3 targets = 90% efficiency vs others at 30-50% with multiple targets very inefficient.
Newsflow of trials: Normally would choose to finish trial, analyze and then report. Still his preference. However they will likely go by cohort but only after a several months so the data has more meaning. Getting efficacy info out by cohort will open eyes as to the potential of the platform.
Discussed factor expression need of 5-50% for Hemo A. Stated that even low single digits may be enough for children.
ARM CGT18 The Outlook in 2018 is a good panel discussion well worth watching. Lots of comments about delivery, packaging and manufacturing as well as references to trials Speakers: Martha Rook, Head of Gene Editing and Novel Modalities, MilliporeSigma (chair) Bill Lundberg, CSO, CRISPR Therapeutics Sandy Macrae, President and CEO, Sangamo Therapeutics Geoff Nichol, SVP, Global Clinical Development and CMO, BioMarin Pharmaceutical Amber Salzman, President and CEO, Adverum Biotechnologies Deepak Srivastava, President, Gladstone Institutes; Professor, UC San Francisco
Known as a ZF company but really our premise is to take groundbreaking science and convert to medicines to treat diseases.
Fascinating middle pipeline involves oncology and CAR-T where we can edit T-cells based on work we did with HIV which shows safety and effectiveness of that treament, and gene transcription control looking at Tau for Alzheimers. Referenced Pfizer collaboration for ALS.
Wonderful this since taking the job has been seeing just how good the platform is.
Like most things its both simple and complicated. The simple answer is eventually the right answer is to edit the disease and correct the mutation or genetic error. With children we feel that genome editing is the way forward. If you can do gene editing you can do gene therapy so we look at it as a suite of capabilities that can be applied to the right medical problem.
Zinc fingers where we can edit any nucleotide is now molecular engineering not molecular biology. The only thing that paces what disease we can go for is can we get to that tissue. DMD/CF is solvable if we can get to the tissue. Encourage everyone to look at new AAVs, LPN.
Response to Q: I'd love to say we could solve DMD this year but we all know the vectors are not there. We have work in nonhuman primates looking to see if we can get beyond the blood brain barrier in a larger species. If we can do that we have a number of CNS targets that can keep us busy for the rest of the decade.
All the companies described how hard manufacturing is on a commercial stage including Phase III, requiring 2-3 yrs advance planning.
Re CAS9 discussion: We use human tools to edit humans...Seems like a logical way to do it...Just sayin.
Under: Been on the sidelines for a bit holding (building) cash. Now that "BIGLEY" has rolled out the tax plan its time to jump in.
Dec 21, 2017 19:06:02 GMT -6
martyc: Looks like you are buying Msft again!
Dec 15, 2017 11:23:29 GMT -6
martyc: The news that Trump called Rupert to congratulate him sure seems to indicate that this is heading to approval
Dec 15, 2017 11:22:23 GMT -6
Under: DIS finally getting some traction.?
Dec 14, 2017 17:08:45 GMT -6
martyc: I took an entry level position in DIS. Will add eventually to overweight when it becomes clearer that the deal will go thru. Can't believe how well positioned they will be. 60% Hulu. 20% of content watched on NFLX they can pull. More in thread
Dec 14, 2017 11:05:16 GMT -6
Under: Great posts on $DIS
Dec 13, 2017 17:50:49 GMT -6
Under: $ROKU Citron on a war path.
Nov 28, 2017 15:11:20 GMT -6
Under: $HAS takeover bid for $MAT?
Nov 10, 2017 16:16:07 GMT -6
martyc: Not looking like the market will provide any discounted opp for SGMO. Call was just too professional and all signs indicate they are on a great path for commercialization. Happy with core but wish I had some trading shs
Nov 10, 2017 9:04:05 GMT -6
martyc: For anyone looking to find an entry point into SGMO, I'm almost hoping is sells off in next few days so I can add more. They are really clicking but the fact they haven't signed new deals might cause some to exit. Watching as I have room for trading shs
Nov 9, 2017 18:28:09 GMT -6
martyc: Been an interesting ride so far. I figured the Bears would be about this good but hoped the O wouldn't look so lame. Another building yr but still possible to get to 8-8 IMO
Nov 9, 2017 18:26:08 GMT -6
Under: whats up with your Bears this year Marty?
Nov 9, 2017 17:35:25 GMT -6
martyc: Hope you were long ROKU. I wanted to see Q first so missed out
Nov 9, 2017 7:08:53 GMT -6