What matters most? Acuity or Duration? What if Opthea was wrong?

I think Opthea's asset is safe, effective, desirable, and very undervalued. But the view of the ocular landscape as pitched by the company looks a bit biased to me. Opthea likes to paint a world view of limited competition focused on duration and not acuity.I am not sure it is a fair description.

A quick overview of the ocular landscape : much more crowded than what OPHTEA wants us to believe.

The field can be broken down into therapies that address the duration of anti VEGF therapy and therapies that address better visual acuity over SOC. you have duration enhancers: like Kodiak Sciences (KOD), then you have gene editing:ADVM/RGNX which represents a new paradigm shift away from monthly injections of anti VEGF ADVM has a gene therapy approach and developed a viral vector that encodes aflibercept and is injected intravitreal which is intended to be a one and done injection; Regenxbio RGNX has developed a gene therapy approach but the injection is sub retinal, is surgical, and carries a small risk of retinal detachment. Also worth mentioning Biosimilar Coherus (CHRS) a future entrant into the antiVEGF biosimilar market.

Is acuity really that important over duration? The market caps of those comps, US$1.5b to $2.5b are x3 to x5 bigger than OPTHEA! .KOD has been awarded the highest MC of all of the companies discussed here but-(because?) their solution will enable injections about every three months.

The million dollar question is what really matters to patients and retinal specialists? A contact of mine (very long ADVM) has listened to several key opinion leaders (KOLs) over the past year that have been sponsored by ADVM. These guys are retinal specialists that run high volume clinics and are consultants for and are involved in clinical trials for RGNX, ADVM, NVS, Opthea, KOD, and Oxurion. .My contact (a doctor) says that one must understand that, in the real world, the retinal specialists’ clinics have been overrun with patients that require intra vitreal injections for Wet AMD. They cannot keep up with the patient volume and the patients do not want to come into the clinic every month for an intra vitreal injection of an anti VEGF. The long term, real world results for anti VEGF therapy do not match the results seen in the clinical trials. There is a progressive loss of visual acuity as measured by letters and confirmed with worsening retinal thickness. Both the retinal specialists and the patients want a solution that gives a longer duration of therapy.

More than one KOL has stated that he does not make a decision on rescue therapy based on loss of letters in an eye because they have all seen a variation of +/- 5 letters in an untreated eye from one month to the next month. They base their decision on whether to rescue or not based on optical Coherence Topography (OCT). If fluid in the retina has worsened, they give a rescue injection.

The field that we are competing against is clearly trying to improve the duration of therapy and does not appear to concentrate on a slight improvement in visual acuity offered by complete inhibition of all three isotypes of VEGF. This requires monthly injections and the retinal specialists have already stated that this is not possible in the real world. There are just too many patients coming into the clinics and there are not enough retinal specialists to do the injections.

What are your thoughts my friends? I am new to OPTHEA so I would appreciate your feedback. Did someone challenge the company in those terms?