Replies to post #6870 on Biotech Values

[nuere]

It will be interesting to see what use OXGN may have of having de Juan on its science board. Perhaps they are already well into preclinical work with his device

[DewDiligence]

Musings on the InnoRx - SRDX marriage:

It’s late on the other side of the Atlantic, so I’ll reply to my own query and wait for isolution to chime in later.

After letting today’s CC sink in for a few hours, I feel even more strongly that InnoRx’s device (invented by Dr. de Juan) and SRDX’s proven polymer technology is a powerful combination.

Until now, the major roadblock to the development of this device platform was a lack of funding. Now, that’s taken care of --SRDX will fund the clinical trials at least through the completion of phase 1.

The advantages of this device are manifold:

1.The ability to elute a drug at a programmable, constant rate over an extended period. This addresses a pharmacodynamic drawback of periodic intravitreal injections such as with Macugen: the concentration in the vitreal chamber is too high immediately following an injection and then becomes too low when it’s almost time for the next treatment. The too-high concentration initially can cause inflammation, increased IOP, and other problems.

2. By keeping the dose level small and constant, possible systemic effects are reduced to an even further degree than with Macugen or Lucentis.

3. The InnoRx device can be implanted and removed with a simple procedure in the doctor’s office. (Hence, the retinal surgeon is properly incentivized, to use a phrase favored by EYET.)

4. Patient non-compliance is all but eliminated as an issue, as discussed in #msg-5158276.

5. The polymer development for the InnoRx device has already been done –it’s the same polymer SRDX made for JNJ’s Cypher cardiac stent. This greases the wheels on the regulatory front because the FDA is already intimately familiar with a key feature of the product.

6. Last but not least, the InnoRx device has the ability to work with a wide array of drugs. SRDX hopes to license the InnoRx device to drug developers but will also work on a couple of in-house drug candidates developed by Dr. de Juan. SRDX’s initial phase-1 trial will use Triamcinilone, but this is more a proof of principle than an attempt to make Triamcinilone the drug of choice in AMD/DME. If the phase-1 trial is successful, we could conceivably see multiple phase-2/3 trials for this device with various AMD/DME drugs in the next couple of years.

--
For background info on InnoRx, please see these iHub posts:

#msg-2346091
#msg-3781650
#msg-3916849

Slides showing the actual device had been available through message #986, but it appears that the linked pdf file no longer exists. I’ll check if there’s a copy of this material available somewhere; if anyone finds it, please post.

[isolution]

isolution: What is your opinion of the InnoRx device?

In the family of local delivery for the eyes, there is the implant subgroup, ie CDS/B&L with Vitrasert (non biodegradable intravitreal implant), Oculex/Allergan with Posurdex (biodegradable implant inserted into anterior or posterior chamber) and InnoRx (coated device implanted through the sclera).

None of these is a miracle solution as always.
First point to adress is to find a stable drug to be incorporated into these devices. It is a good point to be able to achieve more or less constant drug release over extended period of time, but the drug itself has to be stable over this period. This unfortunatly exclude a lot of interesting drug. Drug stability is one of the main issue.

Second point is the formulation work to do to link the drug to the implant. Vitrasert is the easiest for it is a small container, InnoRx based on Surmodics technology and background seems also fine, also for the drug is simply mixed with a matrix, and similar to Allergan that is less experimented. But sometime, for various ingredient incompatibility, formulation can be very complicated.

Third point is surgical placement, InnoRx device seems to be the easiest, Allergan is quite simple also, the worse is B&L for you have to reopen every once in a while to replace/remove the implant. Every time you puncture an eye you have the known risks of bleeding, retinal detachment and endophtalmitis.

Fourth point is side effect of the implant. Once implanted, I don't see much problem with Allergan and B&L except inflammatory reaction due to natural immune system, also some local inflammation due to the sutures (except if the implant carry an antiinflammatory) that can potentially lead to small neovascularisation. The major hurdle for me is the InnoRx. I was interested for a while with the catheter business which are inserted into the circulation. Long-term catheter have well-know side-effect mostly due to the puncture created by the catheter that leads to infections (path between catheter outside diameter and tissues like skin) and leaks (after a certain period of time, tissues surrounding the catheter get loose their elasticity). On that point, I feel very much concerned with InnoRx corkscrew, especially when you know that sclera is not elastic.

Fifth point is side effect due to the drug itself. Long term local realase of certain drug lead to local side-effects as it applies for the whole body. For example, corticoids lead to cataract and IOP rise. The ability to control or modulate the delivery can be an advantage. None of the implants are capable of some modulation without having to remove it.

To conclude, InnoRx implant looks very interesting but definitively less sexy when presented this way.