Just curious, having read this article from June 2022, what makes us think that they will get approval for Antikva.

My concern just stems from the bottom of the article stating.

"Other drugs are in late-stage trials in combination with BCG for the same patient population, including AstraZeneca’s Imfinzi (durvalumab) and Sesen Bio’s Vicinium (oportuzumab monatox). The FDA previously rejected Sesen Bio’s BLA for the treatment of BCG-unresponsive patients, citing multiple issues, including a lack of randomised data comparing Vicinium with an investigator’s choice of intravesical chemotherapy."
https://www.pharmaceutical-technology.com/analyst-comment/immunitybio-first-marketed-drug/?cf-view

There is no comparator in the Antikva trial with any intravesical chemotherapy either, or against anything for that matter. As it's open-label single arm trial, with only Antikva being used. Will this be enough for FDA approval?

I know the prior CRL didn't mention anything about this, but that doesn't mean it isn't a potential issue?

Looking to be convinced wrong on the above :)

Remember, it's not a loss until you sell :)

Regards BLRX, enjoying the run up.

Keep an eye on this one!

Hi Midas, yes I am and happy with the gains recently.

I am thinking we finally start having the speculative PDUFA run up now. Coming in a bit late. Normally this would have started a good month or two ago.

While PDUFA is always a crapshoot, I think the data is very compelling and was well controlled against placebo.

The efficacy data far outperforms plerixafor and the safety appears solid from what we can see.

Given that I think it has a 90+% chance of approval.

You back in Blrx then?

Just FYI, as a general rule, this will be my last reply to you.

So, well let's see, Dror and Eyal did manage to bring in potentially billions of dollars worth of revenue by getting Elfabrio to the finish line. That is no easy feat. If you were in his shoes, would you not expect the same? Ps no need to answer that as per my first sentence here.

They are not desperate for funds, they are pivoting onto new things now that the product has been approved in USA and EU and essentially been handed to Chiesi to sell and with revenues already coming in from product sales (Giacomo Chiesi stated that Elfabrio product was already in the USA which means Chiesi has paid for that), and with the 20M milestone and with royalties to come soon. We know Elfabrio is listed already on almost all the biggest USA insurance companies and is moving through the EU, today we just got Italy confirmation too.

So no need to rest on your laurels, now time to reinvest current cash and new cash into new assets and grow the company in new ways. Sitting around while cash builds up is a nice thing to see in our bank account but it doesn't do anything for you. A new asset(s) will.

If management had not done what they had done in the past, PLX most likely would not exist today at all. I am confident of Elfabrio sales and that the company with Chiesi is going in increase SP nicely.

Note: After GMDA's FDA approval the company convened a special meeting of shareholders specifically to increase the A/S by 50% from 150 million to 225 million and no-one said a peep, in fact people said how great this was as GMDA could make some great deals afterwards, and praised the company and the CEO for being "so good" and "a rock star". Oh yeah and that was after doing a horrendous dilution of 20million shares (+17million warrants) when the OS was at about 80 million, thus a dilution of 25% of the OS. And the vote won with 26million For VS 3 million Against.
Oh yeah and the stock was trading higher for the next month.
Oh yeah and this massive dilution only gets them to "into 2024" as they don't yet have a partner. And more dilution if they don't have a partner inked in the next 3 months. Oh yeah and GMDA stated in their Q1 Earnings PR that the increase A/S was for the partnering as they need a partner and to pay of debt and raise money for operations hence plenty of dilution coming there. Again even moreso if no partner in the next 3-4 months. Oh and their product is only available in the USA.

Meanwhile PLX, Elfabrio is available in USA and EU simultaneously, they have a great partner in Chiesi, they already have cash to 2Q2025, already 1 more year than GMDA not including any new revenues and they want to improve the assets in the company given the high confidence in continued monies coming in. Well shock horror, what a terrible job they've done! So PLX wants to increase the A/S by 27% from 144 million to 184 million, (which is far less than what GMDA did in team of both level of increase and final A/S total), and the world caves in and people start asking for the CEO and CFO to get the chop, that they are greedy and selfish, "dirty pigs" etc and other same ridiculous things people say.

Management has waded through some very tough times and we are still here. The A/S increase is hardly too much nor untoward as evidenced above.

If you don't trust management then you shouldn't be invested in the company, it's just that simple.

Good luck on all future endeavours.

Honestly incredible, that they have the best anit-H.Pylori product in the world with FDA QIDP designation and they are on a Market Cap of 3 million.

I mean, holy moly, I would never have expected that!

Hi Midas,

Only Friday's action I believe and be attributed to A/S emotions riding high.

In general though with regards the Market Cap and hence share price, I think this is the market looking at PLX as a show me the money situation.

Elfabrio is well and indeed approved in USA and EU, but the market may be looking at this taking into account the fact that Chiesi will be contending with Sanofi and Takeda. And while Elfabrio should be fine as clearly many of the current patients are not doing well on the current ERTs that Elfabrio ought very much to take good market share, but there isn't the proof yet, and the drug isn't launched yet.

Therefore I believe the market is waiting for proof of launch which really means sales can happen and then later to see the extent of those sales, before being truly confident that all will be well. Remember the market is highly averse to risk, especially I feel these days with the bear market we've been experiencing.

Let us note that PLX is not the only very recently approve product company to have the SP go down after approval. Recently Eyeniovia, Seres, Biomarin and Sarepta all are down since recent FDA approvals, and Seres is down despite a 125 million milestone payment from Nestle.

All these are in the same situation as PLX, people want to see if you can actual complete getting the product out and selling well.

I'm sure you will also not how despite RDHL having the best product in the world probably on H.Pylori, those sales have been slow on the uptake by general physicians (though it is the top prescribed branded product among gastroenterologist that are in the know).

This said the important difference with the RDHL situation is of course the fact that while h.pylori is common and physicians have many many products to choose from, that is not the case in Fabry, where Elfabrio is the only alternative ERT to Fabrazyme in the USA, but Elfabrio with definite better safety and probably better real world efficacy, and has shown in clinical trials to be better and Replagal in general. As well as this, the physicians are a small circle that all know each other and all know about Elfabrio, so sales should not be a problem at all.

Chiesi has really been a fantastic partner with 200 million already invested and probably another 100 million by the time launch is complete in USA and EU. They have every incentive to maximise sales too.

So that is my take on the market. And yes of course from our perspective PLX is worth far more than 135M market cap at the moment.

In fact, in addition to my post, it might be good to ask BooDog his/her thoughts, as he/she apparently is deciding to wait at the moment before getting in. So one might as BooDog, his/her rationales.

All the best,
Spidey

Why so Midas?

I really don't see the big deal here. As I just posted on ST, apologies my more crude verbiage in the ST post, seems to resonate better with some of the people there. One must adapt:

"So let me get this straight.

Nothing new happened yesterday & some of you just decided to buy into stupidity and fear and go awol?

The company wants to increase authorised shares by 40M as after all potential warrants are conversion (that we have known about for over a year) would be at about 33M AS remaining which is very little, no matter how you think.

They currently have cash at least to Q2 2025, without any new revenues coming in.

Elfabrio has key payer coverage and will be launched in the next weeks time.

Literally all the fundamentals have improved and will further improve going forwards as the only other Fabry option in the biggest market the USA and a far better option to Replagal in the EU.

And it is now, because of 40M increase in 'Authorised Shares', that you've decided to freak out, despite an increase of 20M last time which literally nobody said anything about.

The disappointment is not in PLX, it is in those that give into fear and stupidity."


- Quite honestly the company hasn't done anything strange or untoward.

- Yes they decided to ask for the shareholder vote after the double approvals. But of course they did. They just announced great news for approval in 2 of the world's biggest markets and assumed that given that good news it would be a good time to do the shareholder vote and ask for the usual annual request that comes every single year. This year's requests were no different, nor were the content of the request being odd in any way.

The fundamentals are infinitely better, product has all the main US payers coverage and will be launched in the next few weeks, revenues will immediately start to come in both on Chiesi purchase of drug substance and revenues from sales, which we know will happen as predictables. Milestones hard to predict. I mean the Balance trial patients came into the study on -8eGFR slope despite mean of 6 years on Fabrazyme. Replagal Patients in the Bright study had their eGFR got from -5.9 to -1 which is the same as normal. And Elfabrio side effect profile is better vs both.

And just giving it a second to think about it, the increase of 40 million authorised shares is just prudent and responsible given the low 33 million count remaining they could be at. Nor does it mean that they will suddenly dump all the shares.

Honestly what more do people want from management? Really I'm highly keen to hear all rational suggestions.

As stated I'm not disappointed in PLX, I'm disappointed in and for those that capitulated to fear. But everyone reaps what they sow.

And great to write on iHub again, it's been awhile :)

Best,
Spidey

I would disagree that the once per 4 week is very important for the market potential of Elfabrio, when compared to the equal efficacy and better safety, and probable real world better efficacy.

I think for this it is important to define the 'doing well on Fabrazyme'. Let us remember that from the clinical data, Fabrazyme causes ADAs/immunogenic response in 74% of patients.

So if we assume that doing well on Fabrazyme is in that 26% of patients, then yes, that person would be best suited to switch on to the once per 4 month dosing if/when available.

But the other 74%, even if doing well on the efficacy of Fabrazyme and generally well on more important side effects will still not be feeling great due to this ADA positive activity in their system.

Whereas in the Balance trial, patients with ADA's dropped when on Elfabrio, by 34% and dropped the neutralising antibodies by 55%.

And this is in patients who had already been on Fabrazyme for a mean of 6 years, so these are patients that are tolerating Fabrazyme well/or at least much better than others (clinical trial was in USA and 11 countries outside the USA).

So I think this type of patient (in the 74% ADA) doing well on Fabrazyme, would still be better off on Elfabrio. And this type of patient would already be accustomed to the once per 2 week regimen over many years of Fabrazyme, so it's not like Elfabrio is a detractor on that.

Thus for this type of patient in the 74% with ADAs would be a candidate for Elfabrio. Anyone doing well on efficacy and no adverse reaction and no ADAs would be fine to stay on Fabrazyme.

As remember in the Balance study, TEAE in total were 4x higher for Fabrazyme, and Infusion-Related-Reactions number and rate were 4x and 8x higher respectively for Fabrazyme.

Hi Kronberg, thanks for the message.

First of all I don't think my forecasts and numbers are too optimistic.

I cannot see what patient or physician would not prefer to be on Elfabrio aside from those doing well with low ADA and low side effects from Fabrazyme. As well as the Efficacy and Safety data generated to date, one should also keep in mind earlier PK/PD data which showed significantly more enzyme going into the heart as well as kidneys. If I were a patient I might even demand to be put on Elfabrio if my insurance covers it. And given I'm probably on an isurance that covers Fabrazyme, then I would assume it would cover Elfabrio too.

I believe the above only makes sense. This is my life you're talking about, this is my family I'm going to spend time with. I want to maximise it with a few safety issues as possible.

A timeframe for 50% is too difficult to really predict as I'm sure you'll appreciate.

However I might say, quick uptake of all US & EU Fabry patients that are on very poor eGFR slopes as those recruited into the Balance trial, this being quick for both Fabrazyme & Replagal. Quick maybe 3-6 months post launch and available.

How much of the market would that be, no idea. For fun I would hazard a guess at 10% of the market.

Then we have the uptake of these doing generally poorly and considering the option with the physicians I would put that at another 20% of the market. These coming over a 6 months-1 year period.

Then those that are doing ok on eGFR but are having side-effects from Fabrazyme and want to try Elfabrio to minimise that, another 10% of the market. These 10% also coming 6 months to 1-2 years.

Then some those that are doing well on Fabrazyme eGFR and no big side effects, but that decide that they would like to switch based on the great feedback they hear from everyone else on quality of life. Anecdotal evidence that Elbabrio patients have even started sweating again, which they hadn't done so for years. it might seem small but all these things point to happier patients. And who doesn't want to be happier. These coming from the 1-2 year mark

And that is my highly speculative assumption, though is not to say that Elfabrio would not become standard of care. I only feel this chance is somewhat harder to say as I am not blind to the fact that Sanofi has plenty of expertise and cash. That said I have every confidence in both the Phase I/II and 3 Phase 3 trials data across naive and switch patients as well as all the PK/PD and organ data, as well as Chiesi capacity to maximise the value. They are a Top 50 global company with rare disease ERT experience. Very satisfied.

As far as timing of switch, yes of course this can happen 'in the middle of the year' or at anytime really. I don't quite get why you are focused on the middle of the year?? Curious??

Balance and Bright were both switch studies from patient previously on Fabrazyme and/or Replagal. So yes, any of these patients can switch over to Elfabrio at anytime.

Correct the once in 4 weeks dosing was not approved yet, and based on the clinical data I can see where the regulators were coming from. Not that things were bad, but I don't think it was specifically good enough to get the regulators to agree, especially when they can start the process with the once per 2 weeks regimen that all patients are already accustomed to. So they want more data before approving reducing the regimen by half.

First of all I think that's fine, but more importantly for us, it makes no difference to the revenues as the amount dosed over the 2 week or 4 week regimen is the same and this drug usage is the same. Where of course it could make a difference is for those patients that are doing very well on Fabrazyme or Replagal already, but just want to take less frequent dosing.

I am highly doubtful of a BO, and nor to do I wish it to happen yet, perhaps after a year of sales, and the price would be significantly higher.

But yes, once this shorting nonsense ends and the longs that were in stop freaking out, then we can see the SP take on a true image.

I expect SP to rise nicely even coming into the June strategy meeting, as this may show early indications of Chiesi commercialisation which will spook the shorts.

Just look at GMDA, just the mere suggestion of the upcoming earnings call which may show signs of market uptake or progress in commercialisation efforts has the shorts covering.

I note that yesteday on Shortablestocks, you can see that the short shares available to be seen in that site, when from 750,000 to 1.7 million. So the shorts covering significantly, and which was associated with the 20% increase in GMDA we say yesterday.

So while we will not hear of the amount of the milestone payment which will be made in the next 2-3 weeks based on the USA agreement SEC filing, I still think that much the way the chance of uncertainty and bad news in the market spooks investors tremendously, would expect that for shorts the chance of uncertainty and good news has the same effect on them and rightly so.

The future is bright for PLX and I'm just going to buy more when this nonsense bottoms out. Which could be today, let's see.

Best,
Spidey

Honestly I feel a very big chunk of it.

Compared to Fabrazyme it has at least equal efficacy and superiority in safety. That was in the clinical trial setting. But in the real world Elfabrio would have greater efficacy as we should remember that these patient came into the Balance trial with a terrible mean -8 eGFR slope despite being on Fabrazyme already for years.

I would not understand if being the treating physician why I would not put my more severe/classical patients on Elfabrio due to the efficacy, and I would not understand why I would not put the same classical as well as my other patient on Elfabrio due to the efficacy and safety.

Now this is compared to Fabrazyme.

Now let's consider vs Replagal, where Elfabrio results were incredible both on efficacy and safety again.

Now let us also consider this from a patient perspective. Which treatment would you rather be on? You have a choice of equal or better efficacy with better safety, for a drug that you will take every 2 weeks for the rest of your life and which is keeping you alive.

This is evidenced by the Balance clinical data vs Fabrazyme.We note that in this vs Fabrazyme trial, 97% of the patients completing the trial, 96% (45 of 47) in the Elfabrio arm opted to continue on Elfabrio, and also the 100% (24/24) of the Fabrazyme arm patient opted to initiate on Elfabrio.

The physician and patient community is small and well informed. I expect Elfabrio to make strong sales. To support this we should also note that Chiesi is a strong and well recognised partner, I would expect swift ramp-up with strong continuation of efforts. Time is money. All parties are strongly incentivised to maximise sales.

I would expect Elfabrio to take at least 50% of the US market as it will be the only other option to Fabrazyme, if approved of course, (I think we can ignore Galafold, after so many years they are only treating just about 1000 patients globally). Elfabrio would also take about 50% of the Fabrazyme market in Europe.

But in Europe I would expect Elfabrio to take another 50% from the Replagal market. Hence I would expect Elfabrio to be the dominant player in the EU.

Again just think about, as a physician and patient, why would you not switch to Elfabrio?

While I am not a Fabry patient, I would be almost certain that if my insurance covered both Elfabrio and Fabrazyme, I would most certainly want to be on Elfabrio. The Balance was a trial that was a switch from Fabrazyme, so I would feel very comfortable knowing that this would directly relate to me.

If I were the physician, I might be even more prone to switch my patient because of the clear data proven safety benefits and avoid getting sued in the future.

Again, I would like to hear any reasons as to why not switch to Elfabrio (assuming insurance coverage of course).

Indeed,

I was looking to get to May 1st before buying, but given the consistent upswing in SP, almost 10% in the last day including after hours, and with the 9 trading days to go before deadline. I find it harder now to believe of any reason for it to go down below 1USD.

I notice that there is almost 0% short interest, and I don't see a reason for shorts to suddenly get on board in the next 9 days to take this to below 1USD.

At the same time at this market cap, it still represents a sound investment as they have the funds to get to go-to-market and reach revenues, despite an R/S.

Additionally, given they are above the 1USD price point, compared to where they were just weeks ago, they would actually be in a decent position to ask for the 180 day extension. That would have been highly unlikely just 3 weeks ago.

The recent unusual upswing in SP has changed the landscape for this considerably.

I haven't put in a large sum but something where I am happy for the gains that could materialise. Of course following May 1st, I will look to add more, and for my sake an R/S would be good to see now. Though that possibility looking certainly lower probability given the last 3 weeks.

Quite unbelievable really.

Heck, I don't know what's going on with this stock and this massive uptick in 3 weeks on no news.

Just joined the party.

Very peculiar action though.

Haha, yes indeed and love the twist on the reference :)

Hi rwwine, apologies the tardy reply, things have been a bit busy.

As already voiced here, I too am highly disappointed in management.

I am wholehearted not a fan of Abby. And to be fair while new to the role and getting adjusted to it, her demeanor and tone strike me as someone who trying to convinced others that she knows what she's doing when really she not clear/comfortable at all.

Clearly her decisions have not gone down well in general, what with those 2-3 directors resigning, and then this decision to partner after the management being steadfast in their decision to go it alone up to her arrival.

I realise that launch requires funds, but I think raising some capital but keep all the profits is a much better situation than partnering at this late stage and taking maximum 40% of the profits if they plan to getting a commercialization partner involved.

I am also concerned by her statement " Given the challenging economic environment, to date, we have not been able to raise adequate funding to support our full pipeline and enable a more robust launch of omidubicel, if approved"

I mean, companies in much worse circumstances have been able to raise, and one would think with this first in class therapy for a huge unmet need, just before approval and with all the data in, it would be easier for them to raise. Either this is a lie, or this is just Abby's incompetence, especially after having created a situation such that those 2-3 directors resigned at the same time.

The go-to-market strategy is well defined in terms of centres and the product has obvious benefit. I just don't get this, except if Abby, being as young as she is, has no real interest in properly running the company through the next phases herself, but just get a partner to do it for her as she doesn't know how to handle this.

Then perhaps as you say just line it up for a buy-out and the she can make her money and disappear from the picture. Horrendous selfish conduct if so.

Also killing off the other pre-clin pipeline products and firing one fifth of the staff to extend the cash runway to focus on omidubicel launch I would understand in normal circumstances, but doing that just to extend the cash runway by 1 quarter, wow, sounds like such a great idea.

All seems ridiculous to switch gears at the last moment.

Also having mentioned this partnering (division of profits) and lack of ability to get funds, they crater the stock.

It will take months to find and negotiate with any partner. And with one 1 more quarter added to runway, they are going into any negotiations at a definite disadvantage.

I don't get why they didn't just wait for approval, which at a higher baseline would have upticked the SP to potentially 4 times where we are now. Then at the higher SP do a raise (which I am sure they would be able to do with a just approved product), and then announce they are looking for a partner at a position of strong advantage.

Again Abby I think is in way over her head.

As far as what to do going forward, I mean heck, with 3 weeks to go before approval what more can they do to mess this up?? Yeah for sure buy and run to the PDUFA, but probably sell on the news too, as they will definitely raise straight after (but now at a much lower price point, stupid), because I doubt they will have a partner lined-up within 1 month of the announcement that they are seeking for one.

And if they can raise after the approval, they could definitely raise before the approval, like one month makes a difference??

Or worse based on her communication of difficulty raising above, then what if after approval they still can't raise, and still don't have a partner? So what, they are expecting to make sufficient sales in the 2 months after approval to keep the company going?

So yeah, buy, get to PDUFA then out, then let it drop again with dilution then buy in before potential partnering or buy-out.

Apologies, but all seems a bit ridiclulous.

Agreed, definitely manipulation going on.

The stock, after 6 months of being below 1USD, conveniently over the course of just 2 and a half week manages to get to the 1USD mark within literally days of the 10 day consecutive threshold for delisting, with no material positive news is just too good to be true. Happy for those in, but still looks too convenient without something going on behind the scenes.

Myself still waiting till after I assume something is published by the 1 May, either compliance or still an R/S or 180 extension.

Again this run has been very surprising. Looks like it should get there. Curious of it needs to maintain it for the full ten days or if management will ask for an extension in the case of this very surprising rise.

Again very surprising as nothing new has come out of the company.

Doesn't appear to be insiders either.

Very surprising :)

Another week to see what gives!

Hi Midas,

Indeed the trip up has been unforeseen.

Depends what the situation is vis the potential R/S, but even if it happens the SP will probably not be as low as I might have liked :)

If the R/S happens I think it would probably happen in the coming week, and very latest the week after. Noting that Redhill's recent R/S was 3 weeks before the due date.

Still watching until after the May 1st deadline. Something has to be released by then. Again May will be a big month :)

Just checking my numbers again on the cash runway, and it would be likely longer than I mentioned.

Cash at the moment as expected, but;

end Q2: cash 43 million
Q3 burn of 7 million (= 36 million)
Q3 direct offering +15 million (=51 million)
[Q3 also set a debt financing of 40 million)]
end Q3: cash 57 million (so I assume already took 6 million from the debt financing)
Q4: cash burn I assume about 6 million, but we have not data from the PR nor filing.
end Q4: cash 51 million

If the above is correct then they would still also have about some millions more to draw from the debt financing agreement. Readying commercialisation could cost about 40 million given the small footprint and easier targeting they have.

One hiccup in all this, is that the latest PR and filing doesn't actually inform of the burn, nor if this 51 million ending Q4 cash thus comprises of a higher amount debt already drawn down to make up for the unknown burn, which would reduce the amount to draw down on.

Just listening to the webcast and Phil has mentioned they have invested considerably in their launch activities and building a world class sales team. Hence it would seem they do have some millions to draw down but not the 34 they could have remained.

But they are likely in better financial straights that I had thought in my prior post. My apologies.

This would also make sense with the company guidance that the current funds should last into 2Q 2024. Well past expected approval.

please ignore this message

Hi Midas,

Not to be a spoil-sport, but I don't believe there is any cooking per se. Just some speculation before the earnings report today. Not to say that it will go down after today's report. But I don't expect anything of material value that we don't already know in general.

I would expect them to report that they are on about 50 million USD cash, based on prior burn. But perhaps about 45 million depending on how much they may have already decided invest into the commercialisation plan.

Thus I would at most expect them to have max 20-25 million in the bank at September's expected approval, giving them about 1-2 quarters cash after approval, thus very high chance of a raise directly after expected approval.

While it was a nice bump yesterday, they need another 35% increase to get to the 1USD mark and stay there for 10 days. If the r/s does happen, I would expect it to happen in the next 2-3 weeks. Testing times.

The conspiracy theorist in me was wondering if yesterday's bump is not retail investors speculating on today's earnings report, might be insiders aiming to prop-up the stock buying shares on the open market. But this is just conspiracy silliness on my behalf :) But it would be a one-two punch to show confidence as well as help avoid the r/s and delisting issues.

Seem Zacks has been reading my iHUb post on COMP to CHMP positive opinion conversion analysis :)

"....While we were not able to find any specific studies that estimated the probability of approval for a rare disease candidate after a positive CHMP opinion, a review of literature addressing the topic suggests that greater than 90% of products that receive such an opinion are ultimately approved...."

It was 100% in the last 13-14 months :)

I should really ask them to pay me for this :)

Hi Kronberg,

Apologies the tardy reply.

Aside from the 3 current competitors, I see no immediate important competition coming though the pipeline.

As far as I can see there are only 2 potentials on the horizon but neither look very promising I feel and neither look set to hit the market anytime soon, giving PRX-102 some good shielding from the only potential new agents for Fabry.
The 2 are : 1. Sanofi Substrate Reduction Therapy, and 2. Sangamo Gene therapy

- First For Sanofi, they are currently in Phase III, and have 2 ongoing studies.
The larger of the 2 studies, (114 expected participants), is focused on subjective endpoints of neuropathic and abdominal pain, vs placebo. eGFR isn't even an endpoint in the study.
The smaller of the 2, (90 expected participants), has it's primary endpoint being heart related on Left-Ventricular Mass Index, vs Fabrazyme, Replagal & Galafold. It does have eGFR as a secondary endpoint. But it seems that's not the key item they are going for if they aim to get approval.

I believe Dr Warnock previously referred to the first trial as being heavily delayed in recruitment due to the subjective endpoint. Additionally, with their stated primary endpoints I'm not sure they would have an easy time getting approval. Regulators don't like subjective endpoints and proving a change in LVMI, I recall Dr Warnock also saying takes a lot longer to see any appreciable differences. The study obviously does reflect this at 18 months to outcome, but even then.

Additionally, with the trials being vs placebo and Fabrazayme/Replagal/Galafold, respectively, there is obviously no direct comparison vs PRX-102, which while Balance and Bridge show superiority to the ERTs (galafold is for a different amenable subset of patients), gives PRX-102 some shielding.

Also additionally, based on the study designs, I don't think Sanofi is looking to cannabilise on Fabrazyme, but would look to position Venglustat as a complementary therapy to support in pain and heart indexes. So would not be direct competition for PRX-102 anyway.

Finally on Sanofi, the latest data I can see, related to a 9 person phase 2 trial, of which Venglustat has no impact on reduction of "GL3" which is a different name for GB3 by week 26, hence failing it's primary endpoint. Seven participants continued to the extension study, where changes were said to be observed at 3 years later. Though obviously this is based on a very small number of patients.

So I think we can see that it doesn't look like a great prospect. It also failed a separate trial in autosomal dominant polycystic kidney disease (ADPKD) in 2021, which looked at reducing GL1. Then tag on the Idorsia failure in Fabry.



- Secondly, there is one remaining gene therapy programme that is ongoing via SGMO, but they are taking forever to recruit patients into their Phase 1/2 dose-ranging trial so things would appear to be something like 6-7 years away if all goes according to their own 'unlikely' plan. By unlikely I mean that SGMO has mentioned that they intend to try and save time and go straight to a Phase 3 without even finishing their extraordinarily delayed Phase 1/2, but to me that looks fanciful. Additionally they had already mentioned wanting to do this about 2 years ago after data from just 4 patients. Obviously that didn't get anywhere either. So far it has taken them 4 years to recruit just 13 of the 48 expected enrollment participants.

At the base of this post, I herein post a post I posted :) on the SGMO ST board, for which I only got one person responding to me and didn't really answer the question in any useful manner.

Thus that is my summary on current DD. PRX-102 I feel stands to gain strong market share. I believe based on the Japan Bridge study design that Chiesi and PLX are confident to get both once per 2 weeks and once per month labelling. I believe Replagal will lose out largely to PRX-102 in ex-US. I believe Fabrazyme will lose out significantly in the key US market, as they will lose their US ERT monopoly and I'm sure many patients and their physicians will be keen to try the new drug. I see no important competition coming through for the reasonable future e.g. minimum 7 years out, probably more.

SGMO post:

"Something I don't get. How are they [mentioning they are] planning to do a Phase 3 trial in Fabry, if they have only recruited 13/48 (27%) of the patients in the Phase 1/2 trial? Of which from the new [worldsymposium] presentation it would seem only the first 6 patients have been on the therapy for more than 6 months.

I also see that they were talking of planning a Phase 3 trial all the way back in November 2021 off the results of the first 4 patients in the Phase 1/2 trial. Seems a bit of a small number on both accounts to go straight to Phase 3. Anything happened to delay the previous Phase 3 [plan]?

I don't get how they would go to Phase 3, without at least completing the Phase 1/2? Or at least having something like at least 1 year data on at least half of the intended 48 patients stated for phase 1/2 enrolment.

I get that after the first 9, they go into "expansion cohorts", but still seems a very low number of patients to go straight to Phase 3.

Also I see no eGFR efficacy data which is the gold-standard of efficacy in Fabry.

Seems odd. Please feel free to let me know what I'm missing here.

Thanks!

https://www.fiercebiotech.com/biotech/sangamo-s-fabry-gene-therapy-clears-early-clinical-test-firing-starting-gun-preparations";

Hi Kronberg,

1. Again as I mentioned, Dror had previously stated that only "Active" programs in development are mentioned on the company slide deck.

The fact that OPRX-106 is not on the slide deck therefore doesn't necessarily mean they canned it entirely, just that it is not going through active (read clinical) development at the moment.

2. Just FYI royalties on net sales of 35-40% of sales are exceedingly good terms. Most of such royalties don't go higher than mid-teens.

3. On Pluristem I don't recall, but I can imagine that I did say so. Unfortunately such thinking was based on them actually successfully meeting the trial endpoints for which it seems that management even admitted having chosen the wrong endpoint to lead to approval. Had PSTI achieved the endpoint on their trials I do feel the astronomical market need in CLI, IC and Hip-Fracture would have made a much easier path to the future. Alas that did not happen.

4. Then it seems I misunderstood your timing on this talk of selling. I assumed the fact that you were discussing that now was relating to that happening soon and not in the next 5,6,7 years. As why else mention it at this juncture. But then apologies if there was confusion there.

5. It would no be that the agreements would sign for a future BO, but the terms of a current agreement can limit itself to more conservative terms. Indeed perhaps in time the companies you mention may be interested in buying though.

Best,
Spidey

On another topic of PRX-102 labelling,

I find it interesting that the Japan bridging study is recruiting patients for both the once per 2 weeks and once per month regimens.

Given bridging studies are intended to replicate other studies but with a smaller local ethnic patients, for products and regimens that are already approved in other ICH-GCP compliant territories, this would lead me to believe that PLX & Chiesi are confident for both regimens indications on the EU label at least, probably for USA label too.

Which is nice. Of course confirmation would be on the SmPC following formal EU approval.

Just my personal thoughts, just in case anyone gets confused and assuming I might be saying this will happen :)
(Odd that I now feel the need to specify this when talking about future events outside my control, but hey)

For the record I didn't say that I believe OPRX-106 will be further developed.

I said that I liked the ingenious use of the design of PLX production of using plant cells as the natural delivery vehicle for a drug that will be released only at the site where action is needed, the colon in Crohn's disease. And that I personally hope that funds will be made available for this as I believe it has good market potential as it had compelling efficacy and safety data on a relatively short trial and a great method of administration.

But I mentioned this as a personal hope for further development. Not that I think it will happen necessarily happen.

Secondly, one must think that the deal that PLX got with Chiesi on PRX-102 is a very good deal.

It may be possible that the potential partners were not willing to provide partnership for OPRX-106 in similar or favorable enough terms. They already made virtually no money from the Pfizer deal so they are hardly willing to go for another deal that will seem them have low return on the cost of good involved. Thus I am merely surmising that as they still retain control that they could bring OPRX-106 back into active development and I think it deserves more research. And I personally hope they will, but this is not to say that I think they will. I will not give any specific probability on this, as, as mentioned I have no information on it. But I would like to see it return to the pipeline and I don't see much of a reason why not.

I would think at the very least they could try a moderately sized (circa 80-100) randomised active comparator trial to see if it can match SOC on efficacy, but provide the benefit of oral delivery with no important side effects seen thus far. It's not like Crohn's is a rare disease so a trial of that size would not take too long to recruit.

Separately, I also personally disagree that the company is in view of a sale. If this were to be the case based on expected approval and sales of PRX-102, then this would have been a consideration at the time the USA and ex-USA Chiesi deals would have been inked. If this were the case then it would not make sense for the Chiesi deals to have bothered including the level or royalties and mentioned 1 billion in potential milestone payments.

If management and/or Chiesi would have had BO in consideration on PRX-102 approval, they could have just agreed a simpler deal, just say royalties on net revenues, rather than including a very large 1 billion in milestones on top of the royalties.

The fact that this isn't the case, and both USA and ex-USA deals includes Chiesi paying a transfer price for drug material, paying significant up to 35-45% royalties on net sales, and the 1 billion potential milestone payments, does not have the indication of a company in PLX's place looking to sell at first signs of approvals and 'subsequent decent sales'.

Thus selling the company does not look logical to me at this stage.

Selling would may look logical to me in a few years later after PRX-102 has appeared to reach close to peak sales, when if management want to sell, they would get the most bang for their buck, as the baseline value of the company and their shares would be at much higher place and get a significantly greater return. If their purpose is to get even richer, than they already are, then why not wait a few more years to actually get much richer.

Remember if PRX-102 does do well, it's not like Dror and Eyal for example have to do much more efforts. All PLX has to do now on the PRX-102 program is sell finished product to Chiesi and Chiesi takes care of the rest.

I hope I have clarified my position on OPRX-106, so please do not put words into my mouth, as well as separately providing a clear perspective on why selling the company is not logical to me as yet.

Thus I do not believe there will be talk of BO at tomorrow's ER.

Hi Wgg2,

On OPRX-106. It's not that there has been any new information on that, but the data that came out was already quite compelling, and the whole concept of using the plant cell where the drug is made as the delivery vehicle is simply an ingenious use of the technology when looking at treatments that can affect the colon. As the plant cell wall would protect the drug delivery package through the stomach and the small intestine which has the higher acidity, then passes to the large intestine, but one reaching the colon which is where the pH return to near 7 (neutral), that is where the bacteria flourish that can breakdown the plant cell wall, thus releasing the drug package directly across the area which is inflamed in Crohn's disease.

The fact that it can also be given as a pill is fantastic for these patients.

I merely think this is a great product and deserves more research. Given that have it on hand I think they should progress with it.

I know it hasn't been mentioned in the Corporate Presentations for some time, as Dror specifically stated that they one put "Active" programs into the slide deck. But given they didn't sign any agreements with anyone yet, means they have full control and hopefully soon the capacity to take it further forward.

Just my own thoughts though :)

Best,
Spidey

Following up with my last post, with such a long post I realise I had been too engrossed in looking at PRX-102.

There is of course the sales of Elelyso to Pfizer and Brazil to take into account, which adds about another 20 million to the revenues. Though adding maximum 10 million profit from those sales.

So about 90-100 million in profit from product sold. Still again essentially keeping a 1.4 - 1.8 billion valuation after both EMA & FDA approvals.

I would be keen to see what the analysts think post-approvals.

Hi wgg2, Thanks be to you too for your comprehensive outlook and inspiring me to do a PLX valuation too. I know this is a long post but both providing my thought on cost and then describing my valuation and logic.

In general I think PRX-102 will have one price per mg of finished product. I assume like Fabrazyme it will be provided in 5mg and 30mg vials. Regards the 1mg/kg once per 2 week or 2mg/kg once per month dosing, I don't think that will create a differential in price as that will simply be up to the physician to decide to prescribe it at whichever dosing schedule is best, as the dose itself over that time-period would remain the same.

Purely based on the Balance trial, I do agree that I expect it to be priced at the same or at a slight premium to Fabrazyme, given the significantly better immunogenicity profile and safety benefits, of:
- 4 fold lower Treatment Adverse events
- 8 fold less for Infusion Related Reactions
- Neutralising Antibody (nAb) reduction reduction by 18% (33% to 15%), whereas no real reduction on Fabrazyme (28% to 26%), over the 2 year trial period.
- Reduction of use of pre-medication on PRX-102, which was not seen for Fabrazyme.

Note the EMA COMP has just last week re-affirmed the Orphan Designation of PRX-102, for which Orphan can only be given if it is deemed that the new product presents "significant benefits" over existing marketed therapies. So even in the eyes of the EMA PRX-102 characteristics are superior to the current EU available Fabry drugs, Fabrazyme, Replagal and Galafold.

The advantages of the once per month dosing label for the mild segment, if also approved, this I think we can be a little less sure of, could also warrant a general higher price, due to the increased convenience to hospital, physician, nurse and patient, but not specific to the once per month dosing.

However I think the price will not be significantly higher to Fabrazyme at launch, because a) the price of Fabryzyme is already very high and b) I think they will want to capture as much market share as quickly as possible from the relatively small community of physicians and patients. Of course as is the way with pharma, if the product does well, then they can raise prices later after patients are already on the product and physicians will be more experienced with the treatment and its benefits which will make it harder to switch back to worse performing Fabrazyme, based on the Balance trial patients.

I do think they could stand to take significant market share as:
- The patients in the trial had a mean eGFR of 73 (range: 30 to 126), and a eGFR slope of -8.1 (range -32.6 to -2.1) despite being on Fabrazyme for at least 1 year, however the Balance study patients had already been on ERT for a mean of 8 years prior to enrollment in the trial. So this covers a wide spectrum of patients from moderate to severe, so physicians should be happy to use PRX-102 for all these 2 groups.
- Meanwhile the patients in the BRIGHT study which were of a eGFR slope less than 2, appear to have stabilised with equal performance to healthy individuals, with no new ADAs, reduction of infusion times and no related AEs. So as long as it gets the label, I definitely think a significant proportion of patients and physicians of mild segment whether on Fabrazyme or Replagal will switch to PRX-102. Additionally I would find it interesting to see a segment of patients on Galafold switch to PRX-102 once per month.

One must note that as well as the physician community being small, the patient community is well connected and will discuss PRX-102 which will speed up uptake.

In the EU & ROW, I would expect Replagal to suffer significant losses to PRX-102. The Bridge results were phenomenal on efficacy as well as on safety no new neutralising anti-bodies following switch.

On the financials:

I agree with your 70 million shares outstanding in two years, based on any conversion of notes that most likely will happen, but would be great to see PLX maybe even just pay those off instead of converting. However that is probably les likely as if the SP goes up nicely the note holders stand to benefit more from converting.

I find it hard to take into account all the details of tax loss etc in making assumed valuations and others needed in a DCF model. My method is far more rudimentary :) I simply assume that based on potential Protalix transfer fees and royalties across both EU and USA of at least 90 million USD in first 12 months and then I apply a multiplier of 15 = MarketCap after both EU & FDA approvals of 1.35 billion USD.

My 90 million in first 12 months of sales assumption is simply based on the following:
Top 3 Fabry products are on course to report a 1.8 billion dollar revenue total in 2022.
- on course for 938 million for Fabryzyme
- on course for 520 million for Replagal
- on course for 330 million for Galafold (I know not an ERT, but I think a portion of these opt for PRX-102 if better efficacy on eGFR and pain symptoms, abdominal symptoms and assuming approval of once per month dosing)

Taking patient share from the above, I assume a conservative in first year 20% from Replagal (104 million), and 15% from Fabrazyme (140 million), and 10% from Galafold (33 million) = Total PRX-102 revenue 277 million.

I assume royalties at about 25% for that much total revenue = 69 million + Transfer of substrate revenues about 20 million (about 5-6 million per quarter) = 89-90 million Protalix revenue first year.

Hence 90 million USD x 15 multiplier = 1.35 billion USD Market Cap for the first year

Hence 1.35 billion market cap divided by 70 million shares = 19 USD per share target price after both EU and FDA approvals. (I know I have counted in Japan sales here too, but if they get EU and FDA approvals and now already have their Japan bridging study ongoing, I find it more logical just to count that in for the target price).

However, one must also note that this 90 milllion revenue is essentially 100% profit from drug product as Protalix does not have outgoing commercial, sales and marketing costs or increased headcounts associated to these. Therefore I think one can go with a 20 times multiplier, so getting closer to a 1.8 billion dollar valuation in the 1st year.

As an example if we look at Amicus, who makes Galafold, they currently have a 3.7 billion dollar market cap, that market cap coming from only 330 million projected 2022 full revenue from Galafold, BUT a 180 million dollar net loss in the 1st 9 months 2022, so at least a 213 million net loss for 2022.

So this 90 million of pure profit already places Protalix's financial security above that of Amicus. Technically a 1 million of pure profit place Protalix's financial security above that of Amicus :) I do appreciate that Amicus has just got positive CHMP opinion for its Pompe therapy in EU, but I'm not convinced it's that much better than existing treatments. As it missed the primary endpoint vs Lumizyme, of which Lumizyme itself wasn't better than the initial drug avalglucosidase alfa.

Amicus assumes reaching profitability thanks to the addition of Pompe sales in 2023. But that profitability would be lower than for Protalix and Amicus is sitting at a 3.7 billion dollar valuation!

Protalix will soon engage in more R&D for Gout, but I sincerely doubt that the costs of the Phase I will run anywhere near the profits made, as the gout trials should be faster, at about 6 months active treatment time (vs BALANCE 24 months). And current gout ERT pegloticase managed to complete its registrational phase 3 trial with 225 patients in about 1.5 years total time.
https://clinicaltrials.gov/ct2/show/NCT00325195?term=pegloticase&phase=2&draw=2&rank=2

Note also that we have not counted-in the security of additional capital we should have from the initial Chiesi milestone payments for both EMA and FDA approvals, respectively, which while not from product revenue help the balance-sheet and thus buoy the value of the company as more R&D gets underway.

Essentially though I give PLX a 1.3-1.8 billion dollar market cap for the first year, with Target price at 19 to 26 at both those levels. So add on a bit more time and we get closer to your 30 dollar target price in about 2 years.

After that we shall just have to see how much market share PRX-102 can keep taking from Fabrazyme and Replagal, which I feel will continue over the years. I assume just the above mentioned about 10% from Galafold will be a relatively quick switch-over, but then plateau quickly too as the remaining 80-90% on Galafold will probably stick with it for some time to come due to convenience as a daily oral drug.

Thanks for inspiring to work on the valuation and target price! And thank anyone reading this for their patience if they got this far :)

Best,
Spidey

In addition to my prior post, I just did an analysis of the COMP products noted as "Review of orphan designation for orphan medicinal products at time of initial marketing authorisation - Orphan designated products for discussion prior to adoption of CHMP opinion" similar to PRX-102, as well as the follow-up CHMP opinions.

I am even more convinced we are good for CHMP, virtually 100% chance of CHMP positive opinion, which I know sounds a little crazy but please see below.

I looked at every (in total 14) COMP meeting Agendas covering Dec 2021 to February 2023, and looked at every (in total 13) CHMP meeting highlights from Dec 2021 to January 2023. These highlights of each meeting show positive or negative recommendations by CHMP.

Of the 36 unique medicines the COMP looked at for "Review of orphan designation for orphan medicinal products at time of initial marketing authorisation - Orphan designated products for discussion prior to adoption of CHMP opinion"

3 were noted: "For information"

Of which:
2 applications Withdrawn:
- arimoclomol which had a terrible subjective endpoint
- artesunate for malaria, from B and O Pharma, many generics on the market
1 Rejected:
- omburtamab for Neuroblastoma which was also voted rejected by an FDA Advisory Committee 16-0 because of insufficient data from a single-arm trial and general poor trial design, so lord knows they were never going to get accepted :)

33 of the 36 unique medicines were noted: "For discussion/adoption"
Of which 33 received Positive CHMP opinion

So meaning of the total 36 unique medicines the COMP reviewed for the same matter as PRX-102, 33 (or 92%) followed-on to receive positive CHMP opinion.

AND thus of the 33 unique medicines that were designated "For discussion/adoption", all 33 (or 100%) followed-on to receive positive CHMP opinion.

Given what we know about PRX-102 with Efficacy and Safety, and that it has gone through this process and at the "For discussion/adoption" designation, then I can't see how we would not fit into the 100% follow-on CHMP positive opinion.

Additional review of the 33 approvals:
- 58% (19) - Received CHMP positive opinion at the next available CHMP meeting (usually a few days after COMP review meeting).
- 24% (8) - Received CHMP positive opinion 2 CHMP meetings later
- 12% (4) - Received CHMP positive opinion 3 CHMP meetings later
- 6% (2) - Received CHMP positive opinion 4 CHMP meetings later

So there is a 58% chance that PRX-102 would get positive opinion at the upcoming Feb 20-23rd CHMP meeting. 82% chance in the CHMP meeting in next month and a bit.

But a general 100% change. I know 100% seems surprising but that is the data.

For the sake of completeness, I will add in the only item I can think of which may potential throw a cog in the works. Presently, this would be that for the clinical trials, the drug substance was manufactured in Israel, and then freeze-dried (Fill & Finish) and put in vials in France via a 3rd party, as is common in the industry for cost saving reasons. But since August (after the Clinical Trials were completed), PLX signed a new agreement with their development and commercialisation partner Chiesi to move the Fill & Finish step to Chiesi's own plant in Italy.

So, it mayyyy be possible that the EMA might have qualms about the fact that the drug substance is being bottled at a new location and thus mayyyy want to show some sort of data for comparative structure data to ensure no loss of quality by moving to the new Fill & Finish site. However, this doesn't seem very plausible as the drug substance itself is still being manufactured in the same Israeli facility. And the EMA doesn't usually inspect approved Fill & Finish facilities for each new drug.

Secondly, just to note, Chiesi Farmaceutici, is one of the largest Private Pharmaceutical companies in the world and in the Top 50 Pharma companies in the world in 2020. They have already supported PRX-102 with tens of millions in R&D costs, and stand to make large profits as the PRX-102 global commercialisation partner. So one would hope they would know that they were doing when suggesting to PLX to move the Fill & Finish to their facility, any issues they might bring to PRX-102 approval, they bring upon themselves. Additionally, Chiesi has a separate disease approved rare disease Enzyme Replacement Therapy (PRX-102 is an ERT), so they definitely have the facilities and experience to do this ERT Fill & Finish step.

Best,
Spidey

Without wanting to count the proverbial chickens, I think we are good for CHMP approval.
See below trajectory of recent (Dec 2022) EMA Amicus Pompe orphan approval timeline, then PRX-102 timeline underneath:

March 24 2022 - LoQ
Sept 15 2022 - LoOI

CHMP Nov 7-10 - Pre-authorisation oral explanation

COMP Dec 06-08 - Review orphan designation at time of initial approval [Prior to adoption of CHMP opinion] -> to which COMP adopted a their own "List of Issues" and requested a new OE at next COMP Jan meeting

CHMP Dec 12-15 - Initial Adoption vote - Dec 15 CHMP positive opinion given (NOTE! the COMP request for new "List of Issues" + request new OE did not impact CHMP already having given positive opinion. Most likely as COMP related to orphan status, not general approval)

Additional step: COMP Jan 17-19 - (again) Review at time of orphan designation of initial approval - "for which orphan medicinal product has CHMP opinion adoption"

---------
For PRX-102:

June 23 2022 - LoQ
November 10 2022 - LoOI

CHMP Jan 23-26 - Pre-authorisation oral explanation

COMP Feb 14-16 - Review orphan designation at time of initial approval [Prior to adoption of CHMP opinion]

CHMP Feb 20-23 ----> logical flow, from above would mean up for adoption and positive opinion (even if COMP has a new "List of Issues")

Anybody feel free to review any of this too.
Best,
Spidey

Absolutely agreed, I believe this talk of a buy out is not in the cards whatsoever at this stage. It truly would not make any sense with the trajectory of the decisions made to date.

And with the deals in place with Chiesi and upon potential approvals coming within months of each other for the biggest global markets I can't see what would spur management to go for a buy out.

Chiesi will be paying for product, will pay milestones, beginning with each potential approval respectively and pay royalties.

Personally I also hope as Chiesi throws their weight behind PRX-102, which I believe could truly become SOC, that the gout program will move rapidly and that funds will be decided for more oprx-106 development too which also ought to be quite rapid.

Excellent.

At least I feel I understand this a little better.

Thanks for the posts and for clarifying on this. Much appreciated and hope all's going well with you in general!

Best,
Spidey

Hi Midas and thanks for the reply, but can I just ask a little more of an elaboration as I don't quite fully understand. Apologies in advance for my confusion.

So we have:

NYSE
Shares outstanding = 50.67 million at 1.6USD

TASE
Share outstanding = 50.67 million at 550 shekels = 1.6USD

After moving shares from the TASE to NYSE, we are still at 50.67 million shares outstanding at 1.6USD?

I would have expected this to double the shares outstanding to 100+ million at 1.6USD, which I can understand won't affect SP or M/C, but I don't see how the shares outstanding stay the same?

Or is this effectively saying we were initially 2 pieces of the same pie anyway and were originally 100+ millions shares across both exchanges, and now that we are sticking the pieces together it's all the same?

Not that I am concerned about this as the market is positive about it, just that I'm trying to understand this correctly.

Thanks again!

As in how does the transfer over impact, M/C, SP & Shares Outstanding?

Thanks again

A practical question?

I don't have experience on this, so does anyone know what actually happens when the TASE shares are brought over to the NYSE following the voluntary delisting of PLX Israeli shares from the TASE?

Just curious if anyone has any experience on this?

Thanks in advance!

Finally! This was somewhat overdue and glad it has come to fruition. I was getting a little concerned.

https://finance.yahoo.com/news/redhill-biopharma-healthcare-royalty-agree-120000005.html

At least we don't have to worry about the potential for that debt anymore and things can move on.

Hoping for better pastures coming in the not too distant future.

Still highly frustrated with management for letting this happen, and with HCR for being a less than friendly partner in all this and taking advantage of the situation.

To the future!

As posted on ST,

New Japan PRX-102 trial posted. Excellent.
https://clinicaltrials.gov/ct2/show/NCT05710692

Given the sample size is of 18 participants I take this as a Japan bridging study as required based on Japanese ethnicity, which is excellent news, as this would show the degree in confidence in the potential EMA & FDA approvals.

If one or either of these studies didn't show promise at the clinical data level, then the Japanese authorities would not allow for a bridging study. One can also note this, as this study's primary endpoints are all safety/pharmacokinetic and pharmcodynamic level related.

https://www.clinicalleader.com/doc/meeting-clinical-trial-data-requirements-in-asian-markets-0001
"Japan has implemented the two notifications by assessing each application with foreign clinical data for quality, completeness, and ethnic sensitivity. When a product is unlikely to be affected by ethnicity, the product can be approved without a bridging study. However, if a product is likely to be affected by ethnicity, a bridging study is generally required unless the foreign data contains a sufficient number of Japanese patients to demonstrate safety and efficacy. There is no written guideline describing exactly how many patients that needs to be."

Biologics are dependent on ethnicity.

As another pertinent example of Asian-ethnicity bridging studies, Fabrazyme is currently in a clinical trial for China approval, which is a territory that has the same requirements where ethnicity comes into play. Again where the primary endpoint is safety related.
https://clinicaltrials.gov/ct2/show/NCT05054387

Clearly you didn't even read my post properly. As mentioned these are ADSs that are being changed. Thus, a representation of the BLRX ordinary shares on the TASE. Hence the Board of Directors can amend the proportion of the ADS representation.

This has the effect of an R/S, but in legal terms this is not an R/S, hence the shareholders/stockholders are not needed to be involved in the change of ADS ratio.

This was made clear by the provision of the link I gave, which showed the change in ADS ratio the BLRX management already did in June 2019, acting LIKE a 1-for-15 R/S.

Copy/pasting again:
https://ir.biolinerx.com/news-releases/news-release-details/biolinerx-announces-change-ratio-american-depositary-shares
" its Board of Directors has approved a change in the number of its ordinary shares represented by American Depositary Shares"
"The change in exchange ratio for the ADSs will have the same effect as a 1-for-15 reverse stock split of the ADSs"

If you're not even going to read things properly then there is truly no point in discussing with you.

I also find it extraordinary that someone having "no investment in this company" for your initial impolite response to be even more bizarre and untoward. And again even moreso, given your appearance on this board out of nowhere, and a response that was posted within 40 minutes of my post, hence reading my post within 30 minutes of posting. Yes, very odd indeed for someone who has no investment in this company.

But whatever you say, good luck whoever you may be, as someone with no investment in this company.

Shocking! I am saying nothing false at all good sir/madam! If anything your post betrays your lack of experience, as I will expound on below.

I assume you are significantly down on your investment hence the impolite and short retort.

First of all, yes of course there is the initial 180 day grace period, followed by a potential 2nd 180 day grace period, if the exchange is satisfied with other conditions, for example a minimum 50 million dollar Market Cap etc.. (Note BLRX's current NASDAQ MC is at 39 million).

This said however, I have never seen a company go the full 12 months of grace period based on the issue raised being the minimum bid price which is in essence a very small aspect of the ability of a company to stay on the exchange. Hence why I reiterate, in my experience this usually occurs about 3-4 months post the receipt of the notice.

Additionally, per the BioLine PR itself, the company plans to regain compliance on the minimum bid price by the end of the 1st grace period.
https://ir.biolinerx.com/news-releases/news-release-details/biolinerx-announces-receipt-nasdaq-minimum-bid-price
"The Company will continue to monitor the closing bid price of its ADSs on Nasdaq between now and May 1, 2023 and seeks to cure the deficiency within the prescribed compliance period. "

This given we are at the 3 month mark of the initial (6 month) grace period, and there has not been a significant upside to the SP, requiring an approx 50% increase from current levels, then with 3 months left to go until the end of the initial grace period, then I would expect that unless there is materially significant news, there is little reason before May 1st, for there to be a 50% increase. Not including the time required to execute the ADS ratio change (note this is not an actual R/S but an effect like one). Especially since intrinsically things have actually improved within the company's situation since end-September 2022 when the SP initially fell below the 1USD mark.

Again the potential ADS ratio change (R/S) simply being a financial instrument to prop up the Nasdaq SP. The intrinsic value of the company and its assets remain the same. So for the company the decision to do an ADS change (R/S) when the minimum bid price is the only issue is relatively logical, simple and straightforward.

September PDUFA would also be even after the end of the potential 2nd grace period. Thus it would make very little sense for the company to drag out the process, unless of course there is as yet unknown positive news upcoming before these dates.

Wrong sir/madam. The BLRX ADSs are a representation of the ordinary shares that BLRX has on the TASE. Hence a change to the ADS ratio would require the approval of the Board of Directors, Not the share/stockholders. This in effect acting like an R/S on the NASDAQ while the actual number of ordinary shares of the company on the TASE remain unchanged. Clearly there is some experience you are lacking.

PS, I may bring to your attention that BLRX did already do an ADS change (R/S) in June 18 2019. The effect of a 1-for-15 reverse stock split.
https://ir.biolinerx.com/news-releases/news-release-details/biolinerx-announces-change-ratio-american-depositary-shares
" its Board of Directors has approved a change in the number of its ordinary shares represented by American Depositary Shares"
"The change in exchange ratio for the ADSs will have the same effect as a 1-for-15 reverse stock split of the ADSs"
So it's not like management doesn't have recent experience doing this.

Secondly, responding to your second message on the level of cash BLRX has, yes indeed you are quite correct and of course I am aware of this as I am watching the company as I do believe in the product. One would be an idiot not to see the clear clinical benefit of Aphexda. However as you will know of course, the cash position of a company has little weight vis with the SP, as the SP and more importantly the MC reflect more the confidence the market has in the company's situation going forward. So dilutive or non-dilutive, your statement on the cash reserve gives comfort for dealing with things to come but is essentially irrelevant vis MC and the SP, as is obviously evident.

Thirdly, I also find these situations rather amusing, where people believe that presumed +ve and -ve posts on informal chat forums actually have a meaningful impact on SP. Articles on SeekingAlpha being a recognised space for investment advice can cause such issues. But chat boards like Investor'sHub? Surely you can't be serious. With the hundreds of thousands of posts per day it would be incongruous to assume that iHub posts have any impact whatsoever. If so, I could just invest and write positive comments all day. Nonsense. Additionally, you will of course note that I am by far and away not to be the first person to have discussed the potential R/S. And if by some stretch of the imagination you feel the company itself is taking their financial strategic advice from posts on iHub, I do hope for all our sakes that you are mistaken!

Meanwhile, while I appreciate you may disagree with any statement made in any post, please observe a minimum level of decorum as befits strangers communicating on an open platform. Nothing I have said is false in any manner whatsoever, who knows it seems like you may have even learnt something new. You're welcome.

Finally, in evidence and in my most recent R/S experience to boot, which fellow poster Midas can corroborate, Protalix Biotherapeutics received a minimum bid notice in August 2019, and 4 months later December 2019 they executed their R/S.

So yes, what I mentioned was based on my experience and nothing I have said is false. If there are things where you yourself don't know what you're talking about I might ask you to please refrain from putting forward unfounded negative drivel.

Thank you.

Not only that but seeing as they got a delisting notice on the 8th November 2022, then 8th Feb will be the 3 month mark.

In my experience a R/S usually happens about the 3 month mark after the notice.

I like the product, but with R/S potentially on the horizon I am waiting on this one too at the moment.