SurModics Inc (SRDX)

[Democritus_of_Abdera]

2007 ARVO Meeting – Adamis Presentation....

In the April 2007 conference call, Bruce Barclay said that the ARVO meeting was a big meeting for SRDX. I agree. I am at the meeting now (it will last until Thursday), albeit my interests primarily relate to my personal research focus, rather than SRDX’s fortunes. Relative to SRDX’s interests, there was a high profile talk by Anthony Adamis, President and CEO of Jerini Ophthalmic (formerly Chief Scientific Officer of OSI Eyetech) entitled “Future Directions on Anti-Angiogenic Therapy”. Adamis focused upon three strategies for enhancing the current standard of practice regarding Lucentis treatment of ARMD: 1) reduce injection frequency, 2) increase efficacy, and 3) lower price. He emphasized more than once that drug delivery is the key to future progress.

Some of the points he raised in his presentation were:

1. A higher affinity anti-VEGF binding agent might allow one to reduce dosing frequency. He suggested that injections at a 3 month interval might be feasible with VEGF-Trap (Regeneron) because of this affinity difference.

2. One might use encapsulated cells engineered to express VEGF-inhibitors. (He didn’t mention a particular company, but I know of at least one related initiative in this direction... that by Neurotech employing encapslated cells secreting ciliary neurotrophic factor (CNTF)...).

3. Tyrosine kinase inhibitors might be more amenable to standard drug schedules (again, no names, but Gleevec comes to my mind).

4. Gene therapy via transfection of the intra-ocular ciliary muscle to produce an anti-VEGF protein is a possibility (my notes don’t reflect the precedent that he mentioned in this regard; however, I know that this approach has been used in experimental situations (see Bloquel C et al., FASEB J 20:389, 2006)).

5. Drugs could be released slowly from an intra-ocular implant (Adamis mentioned his experience with Mucagen in microspheres, but there are several other examples...SRDX’s I-vation-TA being one).

6. The pharmacokinetic compartment represented by the eye might make siRNA strategies uniquely attractive (although, I am not a fan of siRNA because it often down-regulates rather than completely inhibits expression of the target protein, and its efficacy depends upon factors which I do not understand, but suspect are hard to control in a clinical setting).

7. Adamis argued that combination therapies are attractive candidates for next generation paradigms. He mentioned some of his studies combining photodynamic therapy, VEGF binding, and steroid treatments (treatment sequencing made a difference). He also suggested that drug combinations that inhibit both PDGF and VEGF might be attractive (that’s one reason that I am interested in how the Gleevec/Lucentis trial mentioned in #msg-17653474. turns out).

8. He discussed his current initiatives with Integrin alpha-5-beta-1 inhibition (i.e. JSM6427), but argued that the mechanisms of action do not make it a good drug target for inhibiting retinal vasculature even though it is a good target for inhibiting tumor vasculature (at least that is what I think he said...even though, upon reflection, I cannot imagine why the CEO of a company developing this compound would say that before all the data is in .

9. He suggested that more research should be directed towards studying immune factors; in particular, he called for studies on Complement Factor H’s involvement in ARMD.

10. Finally, he argued that the Ophthalmology community should be focused upon vessel normalization rather than vessel regression when treating ARMD. He high-lighted the fact that VEGF does more than serve as a growth factor for blood vessels, it also is a neuroprotectant. He raised the spector that anti-VEGF therapy might compound the adverse effects of retinal hypoxia because VEGF is an important endogenous factor preventing neurons from entering apoptosis after an ischemic challenge.