Good to see a few informed posters still here. It's hard to judge the value until we know the full story behind STRIDE and what the FDA decides for a path forward. They haven't even provided a timetable. Yes, risk is up, therefore value is down.
If what they are saying is correct, Ampion worked well enough to have the same value it had before the saline debacle, but lower NPV. I'm guessing that if the approval timeline is now delayed another 3Qs, we stay at this value or maybe somewhat higher after guidance is announced. A rolling BLA announcement will send this back to $8 in one day.
This is a drug that is I've stated before as worth staying aware of. It is the only compound I know of with demonstrated normal, hyaline cartilage regeneration properties. Stem cells also work, albeit with additional trials needed to assure broad, repeatable efficacy. TPX-100 has just completed Phase II enrollment, so it's still a few years off as well. Hopefully Ampion will be in final approval stage by the time Phase III starts. Note restriction to bilateral OA.
"OrthoTrophix, Inc., a privately held biopharmaceutical company, announced today that the Company completed subject enrollment and all scheduled dosing in its Phase 2 clinical study of TPX-100 in subjects with bilateral osteoarthritis (OA) of the knee. The Company initiated the study in early 2014 (Press Release on February 20, 2014). One hundred fifteen (115) subjects have completed all scheduled intra-articular injections. The last subject’s last visit of the clinical site is scheduled inApril 2016, and the study results are expected in mid-2016."
I haven't seen anything beyond the PR 2014Q3 stating it was available for another 12 wks. My guess is that a Phase III for 1 yr will be needed to show stability as the disease progresses slowly.
Last year I referenced non-Ab treatments for DME in "Treatment of DME Beyond Anti-VEGF" in RetinalPhysician. Optina gets a mention in "other". Lots of good compounds even w/o what may be a leader, Fovista.
Great analysis. Even changing the ratio of patients/eyes: about 66% were 1 eye/patient doesn't change the numbers much. Generally, anything less than 5 letters is noise and insignificant. That is one problem with such a short trial in DME or AMD.
The problem remains it will quite expensive to develop and there will already be at least 1 very effective therapy to combat refractory patients by the time someone begins a pivotal trial with Optina. Also, a longer study is needed to see if the results last - the drug does nothing to stop continued growth of new, weak blood vessels, so it may just offer temporary symptomatic relief.
Agree - based on the 20wk data release. As of late last week, some were told the data was still with the biostatisticians, but with no date given for release. That might be due to a few patients being late for the final exam. Other, equally good sources, were told the data was not going to be released prior to FDA meeting.
I still believe that would be a mistake, at least with top-line numbers, including WOMAC A changes just for the Ampion arm. We are owed that at least, otherwise, their continued statements that the data look very good have no data to support them.
Given that Optina was dropped entirely from the Oppenheimer presentation, it's more likely that it is the next "asset" to get disposed of to prepare for an acquisition.
I doubt that any serious investor, particularly the institutional ones are in any way distracted, though communication (including unrealistic statements about market opportunities) are often less than stellar.
I'd disagree about Ampion's future, per comments elsewhere in this thread. Short term, yes many will give up. I'm not one to panic, but I could also be wrong!
Yes, the DD team must have provided a favorable report and has seen as much as the FDA has, if not more. Details of STRIDE will probably show some advantage to MI vs SI, but the sources of variation still need some work.
The 505b(2) path is useful, but complications from fat-sensitive distribution, the limited responsive cohort, the need to perform longer term studies and Fovista all limit future potential revenue. They promoted 505b(2) far more than was practical. In reality, many repurposed drugs still require convincing evidence from adequate powered trials for approval. Optina could not complete enrollment even for this trial. So, expensive trials and high commercial risk will indeed provide lower NPV for Optina.
Stuart is knowledgeable in this area. He has a lot more credibility than most here on retinal diseases and therapies.
BMI correlates with Optina efficacy due to distribution factors. It is highly fat soluble. Only low dose is efficacious. But, dose and exposure are completely different factors. The BMI-dependent dosing was suppose to normalize exposure. Since the results are not uniform across BMI in this study, that dosing regimen did not work well.
Much more work needs to be done, as high expense. Meanwhile Fovista had amazing efficacy and is already Phase III for AMD. Extension to DME is trivial. As I stated earlier, 6 letters in 3 months is good, even compared to anti-VEGF. But, this does nothing to stop continued angiogenesis and any potential partner knows that. An adjunct therapy at best, but potentially having some value.
Honestly, we have to wait for the 24 wk data and I'm as impatient as most. If the variance is due to a few sites/clinicians it has to be handled sensitively. If it's due to disease variability (compartmentalization coinciding with injection location) that can be used in a new trial design. What we have been told (and via rumor mill) is that the drug had good results. It's also worth noting that saline effects decline with time, so the 24wk endpoint may have better comp-values than 20wk (but probably not enough to shift p-values).
The FDA understands all the factors. Starting a BLA with what they have and running a confirmatory trial concurrent with that is not an impossibility. That would be huge. Comments from physicians after unblinding would be very helpful. So, there is a market, at least one interested partner and an efficacious drug that is competitive with current therapies and pipelines. There is more chance of upside than downside.
Most of us have been requesting some good news and they did deliver.
Note the response: From $2 to $2.5 vs $8 to $2. It corresponds to the relative value of Optina vs Ampion.
There are already predictable, and useless, comparisons to REGN etc.. As stated many times before, the effect is interesting and useful in a small population. That is due to an orthogonal MOA vs anti-proliferative growth-factor inhibitors. For those new to DME and AMD, it is angiogenesis that drive the edema and inflammation. Reduction of leakage by Optina clearly helps a small subpopulation.
The term REFRACTORY refers to those patients for whom anti-VEGF treatments have led to less-than-avg responses. That is due to protection of vessels with pericytes. anti-PDGF compounds strip those off, leaving the vessels susceptible to anti-VEGFs. That is the concept behind Fovista and has been validated in Phase III trials. Gains of more than 3-lines (+15) are seen for many patients. THAT is an effective drug for refractory patients. But, the time scale is different, and for Optina to show +6 in 3 months is pretty good!
But (always a qualification) only for a subset of patients. That is because Optina must be delivered at low-dose at the site of action and it binds to fats so controlling the volume of distribution and exposure to the retinal tissue is difficult. The BMI-weighted dose was supposed to normalize that. It did not. Still, there is only a certain group it was effective for.
Can Optina ever be a commercially successful drug? It will take another expensive trial, lasting 6 mth to 1 yr to determine that. Meanwhile Fovista is very likely to be approved for AMD and DME. It is backed by Novartis. Squalamine is an interesting option (topical eye drop formulation) that replicated Fovista efficacy gains vs Lucentis control, but in a small number of patients and without strong p-values. Fovista's were unquestionable.
So, nice to have this. But it is AMPION that matters.
There appear to be different comments investors are hearing, whereas a simple statement updating progress would serve shareholders well. If the results are still in analysis mode, they should state that - everyone knows that the 20 wk analysis occurred up to 1 wk before they announced endpoint failure. There may have been delays due to a few patients, etc. But, it's "overdue" from an investor perspective. That is one of the key jobs of a CEO.
If they have no intention of releasing results prior to FDA discussions, that is their prerogative, but it help to understand the rationale. The CC call did say the results would be shared: in scientific conferences and journals (if I recall correctly). Those are months away.
If the company is stating that the results look positive from one source, but are still being analyzed (from another source), why can they tell it is "positive"? A simple statement that initial indications show strong efficacy, but the full results are still being properly analyzed and will be made available...?? Or, we feel strongly about the drug's potential given the data we currently have from STRIDE but need to refrain from detailed comment until we meet with the FDA within the next X days.
Patience is always required with pharma development. But, management has made many promises about when Ampion would be brought to market. They have failed 2 out of 3 times in Phase III. What leads them to believe next time will be different?
Of course not. But good news is always reported. Bad news or "no news" because of ambiguous results are not. Any experienced biotech investor understands that.
Ampion still works. The company does not.
It's a crisis management issue that they don't understand - lack of communication and poor communication hurts shareholder value. It may very well be that 24 wk data was worse than 20 wk and Ampion no longer had a clinically significant effect. It only has to drop 5-10% from the minimal 40% to equal saline.
No news on Ampion efficacy. No news on resolving robust saline results. No news on when FDA meeting will take place. They can't afford to refinance at these levels and only have a 18 months of cash left.
Withholding key results is poor management as there is no other recourse except to interpret them as poor.
Assuming they did not blatantly lie, Ampion still beat the usual saline response. If they did lie, then there will be real lawsuits, with a copy of the CC recording as evidence. They can't be that stupid. Perhaps there is another reason for hiding the data. In the case of Optina, the FDA did require additional tests, at least according to MM. Still odd though as the even released STEP data, as bad and convoluted as *that* was.
Thanks - reassuring, even in a small way. The big guys would have led the way if it had merit.
Exactly. Step up for STEP.
Interesting why they are just now going after *that* disaster. I think it's $100K loss, rather than shares. If I thought there was substantial evidence of fraud and that we had no other way of recovering, I'd consider it. But none of the big investors from that timeframe bothered with it. There is no new evidence. Also, still believe that even these guys still have a final gasp of air left in them.
Competitive monitoring is useful to gauge product value. Value is derived by discounting potential cash flow several years out, which means having a reasonable idea of competing products at that time. That factors into any bid. MM routinely shouts about the unmet needs in OA, quoting only current therapies. Not once have they acknowledged many different therapies at similar stages of testing. So, I continue to monitor the field. Certainly SC for OAK has a large number of studies, most of which have demonstrated far more efficacy in cartilage growth than what Bar Or was trying to sell.
Completely agree with you about the added need of knowing what the FDA will demand and how AMPE can possibly survive until BLA approval without more capital. The most immediate concern is where is the 24 wk STRIDE data? The strength of the Ampion arm should at least provide some idea of how valuable this actually is and whether anything was learned that could lead to a better outcome on the next attempt.
MM said everything was on the table. What's real is another matter. Yeah, dumping for $8-10 (my estimate, since another Phase III is needed) would be fine, but unlikely IMO. Partnering, with an upfront payment would be a relief since it keeps them operational, provides expertise and validates the drug (pharma would have done more DD than even the FDA). But, at the risk of long term gains (and management egos...)
What was Einstein's definition of insanity? Something along the lines of repeating the same experiment with the same conditions and expecting a vastly different outcome....
The drug is in a suspension. Low T's cause certain excipients to form films, adhering to the walls of the vial. Without resuspending, the amount of drug delivered to the syringe is decreased.
Yes, that's currently true, but too many companies are pursuing it for it not to be feasible. Also, it is 1-time (or few) curative treatment, so has a much higher value.