From Ivillage
Unfiltered Notes from SGMO BIO CEO Presentation
Covers everything but first minute or so....
* Dominant IP
* Significant partnerships and strong B/C
* Non-dil cash flows
* Start 2008 w/81M
* 2007 prosecute 2 P II, burned 15M, 14M in 2006
* Lev techn in non-core areas, keep low burn rate
* Type of techn platform
* 99.9% small molecules, MAB, recombinant proteins function at protein
* RNAi at RNA
* ZFP only one at DNA
* Target # per cell is 2 versus antisense/RNAi 10,000s of RNA, 100,000s
* Can get singular specificity
* Imp re tox
* Can stop things from happening, like RNA,
* Can also turn on or modify
* Drive phenotype can’t do downstream at RNA and protein level
* Fn at DNA level diff value-creating outcomes
* SGMO wons 100% therapeutic opps, value will accrue signif, dominate IP
* In plant ag, lab reagents, protein MF have partnerships
* Next 6, 10, 18, 24 M more value attrib to otger programs
* Pro dev pipeline
* Most adv SB509 P II
* Summarize 2 new programs take into clinic 2008
* DN, diabetes epidemic, exported Western diet
* Head of Bus Dev, in Japan
* Chinese govt estimate 2% of Chinese pop have diabetes
* That dwarfs the US
* Diabetes worldwide and expanding
* Half of diabetes start hving nerve loss, can lead to loss of sensory and motor nerve loss
* No drug can stop this loss of nerves, except good ctl of glucose
* Only symptomatic, anti-depr, NSAIDS
* VEGF potent neuron-regen, neuroprot and angiogenic
* Direct activity on neural and glial cells
* Activating endogenous gene inside body good, need multiple isoforms
* Publ extenstively
* DNA plasmid, circle of DNA, encodes ZFP to target VEGF-a
* Inject into lower leg, skeletal muscles, ZFP gets transcribes, activation domain, ZFP target VEGF gene and expresses, secretes normal isoforms in normal ratios
* 1st NCV, neuroprot and neuroregen
* Took into clinic
* Showed topline at ADA in Jun2007 Chi, Sep2007 Soc N/S mtg
* Not just neuroprot, but also neurogenerative
* Not by looking at qualitative, high level
* Have very specific quant measures
* 1st is QST, allow physician to analyze reaction to vibration
* NCV
* QST by Vibratron, randomly to button A or B, randomized, handle if think is A or other if B
* Computer randomizes and moves to lower level, miss twice and that is the QST level
* Accrued, mild to mod DN, randomized to SB509 plasmid or placebo
* 10 patients on drug, 10 placebo
* One Tx Day 0, followed for 6 M
* Saw 25% improvement from baseline in QST vs slight deterioration in placebo
* On avg 5-10% deterioration per yr untreated
* QSt was stat sign, gives us courage where headed
* Other endpt in P Ib is Nerve Conduction Velocity
* How long from one electrode to another, Tx day 0
* Impr 2m/sec, clinicians 1-1.2m/sec considered clin sign
* Sensory nerve (sural) 1.35m/sec
* Look at 180 days
* Slight erosion from one time Tx
* In P II, multi dosing, 0, 60, 120 days
* Compl accrual DB, PC multi site, randomized
* N=110, 2:1 randomized drug to placebo
* Collect brought range of clin data
* Primary EP QST, NCV, ENFD&R, TNS
* Final data analysis mid-2008
* Primary data analysis at 180 days, some time this summer
* Then break blind, present in 4Q2008
* Imp event for us, well-pos based on P Ib
* Other 2 clin trials
* P II mod to severe DN, Blocked Nerve Regen
* 3 in P Ib w/BN had some effects w/one Tx
* N=45 30 SB509, 15 placebo
* 2 dose 0, 90 day
* IM 30 mg in each leg
* Clin EP NC regen, recovery of amplitude and NCV in LE nerve and distal
* QST and TNS
* Accr 1H2008
* Possibly interim at ADA
* SB509 P II Stem Mobilization Trial
* Sign incr in progenitor cell circulation, interesting observation
* Ongoing, when data avail present
* Also help explain mech neuroprot and neuroregen, not jus in clin, but animal in severe settings
* Guided to start ALS P II, neuromusc, vasc fns of SB509
* Shows what in lead programs
* Two pre-IND programs
* Talk now about ZFP attach diff protein attached to ZFP, enzyme to change/modify
* E.g. cancer, glioblastoma, working w/City of Hope, they dev cell line to target
* Refer to website w/video in animal cells IL-13 traget
* Well-established mechanism
* Post-surgery all get steroids re brain swelling, can shut down immune system cells
* We have succ knocked out gluticosteroid receptor, more later in 2008
* Other re nuclease modification, HIV/AIDS, CCR5 re CD4 receptor, if I is defective then can’t get HIV/AIDS
* Permanently resistant to HIV/AIDS, showed at ICAAC, working w/U of P
* Function at DNA level
* Bus strategy focus on core science and areas where DNA level differential advs
* Establish as 1st new thera platform dev, post human genome era
* Look for pts if signif value inflection
* Post P II, seek partner to go to P III
* Lev IP and science outside ZF therapeutics
* Dow Agro, announced 2,5 yrs ago
* If Dow Agro exercised commercial license, 27.5M over 3 yrs, said they would
* Get milestones and royalties and portion of sublicensing
* Achieved multiple scientific milestones
* Jerome Peribere spectacular AD presentation 5Dec2008
* Jerome presenting at GS Agro conference
* He will make imp remarks re collab and announcements in that area’
* Already sign milestones, gene reg
* Enormous # of targets
* Knock out 1 gene could have huge impact
* Thousands of targets ID
* Mkt size enormous, continue to be new prods, targets
* Such as herbicide resistant
* Opportunity for them and lev into multiple areas
* Will exercise commercial license and broadly sublicense in agro field
* Get lots more visibility aftyer exercises commercial agreement and sublicensing
* No models factor in Agro
* Imp collab w/Sigma Aldrich
* 13.5M u/f
* Academic and lab commercial reagents
* Double digit royalties
* Sublicense 50% 1st 2 yrs, 25% thereafter
* Addit
* Lic 2M, etc.
* ZF nuclease to do knockout in CHO cells re MAB M/F
* Collabs w/many, most recently Genentech
* Unlike Dow and SA exclusive, these are non-exclusive
* Work w/any of the companies
* Finite # of targets
* COGS low once down other
* Significant downstream out of modified cells lines
* Fin summary
* Fisc resp
* 2 P IIs, finish accrual P Ii 16M in 2007, 15M 2006, less than 15M 2005+2004
* No debt, no warrants, no converts
* 2008 objectives
* Complete P II SB509
* SB509-601 DN mild to mod
* -701 BN
* Compl accr Stem Cell Mobil
* 2 new, glioblastoma and HIV CCR5
* Cont to adv ZFP thera
* Preclin SCI, TBI, stroke
* Strategic collabs
* ZFP thera.DN
* Increase visibility Dow Agro
* 55M byYE2008
* SGMO is quite uique
* Science very powerful
* Drive outcomes can’t do at RNA, protein level
* Have S/H own thera, lev into agro, regents, prtein <m/f
* Dominant IP helps do deals, can’t circumvent us
* Q&A
* Q1: SB509, variability of response, robust across all 10? In era of safety obsessed FDA, off target issues oncogenes?
* A1: Present full P Ib, ADA in Jun2007 SFO, present interim kinetics and variability. If look at QDT, 10 patients, 10 placebo, get stat sign, shows lack of variability. VEGF as angiogenic, disc w/FDA. Direct injection in local muscle, measure and take blood, measure VEGF, not above normal levels. Canary in coal mine are changes in eye blood vessels, look at retinal scans. No SAEs.
* Q2: Charles Duncan, predictive value in P II? Sense what needed by FDA re clin benefit? Same measures sufficient?
* A2: Predictive elements. Go back and think about DN and painkillers. Approved on visual analog scale of pain, 0 to 10. What happened that morning, that afternoon, ‘m a 7, chock full of placebo effects. Highly quant measures, highly predictive, not only highly quant, also pretty tight response in placebo and treated group. EPs re approval, several yrs ago Genentech took NGF in P III, not succ. In process, said not painkiller, looking neuroprot, neuroregen. DN is deteriorating disease, 5-10% per annum. If just main, that is sign benefit. FDA said 1-1.2 impr in NCV. Anything about 8-10% in QST is clin benefit, we get 25%. Collecting these data, large variety of data. Relevance and magnitude drive P III design and EPs.
* Q3: In SOD1 ALS tested?
* A3: Talk more, but not using that. Not a critical path to start trial.
* Q4: Injecting plasmid, FA concern re gene therapy, direct DNA. What re safety DB to register?
* A4: Plasmid around long time, multiple clin trials. FDA said don’t need lifetime, LT plasmid studies. The onerousness is not, Relatively straightforward.
* Q5: Sample size driven by efficacy expectation vs LT safety issues?
* A5: Yes, driven by size, to reach stat sign.
* Q6: Put up 95% confidence intervals. Imp to see which are or not.
* A6: They were presented at Soc of N/S. |
