Replies to post #3673 on PROTALIX BIOTHERAPEUTICS, INC. (PLX)

[midastouch017]

Conclusion

PLX's Fabry program has finally arrived at a finish line of sorts, with the completion of BALANCE, PLX's only randomized, controlled (with an active comparator control vs. open-label without a control) phase 3 Fabry trial.

It all goes well from now on, the company plans to resubmit their application to the FDA in the second half of 2022.

Needless to say, the company and the investors share a great hope for PRX-102's market potential (up to >$1B in potential milestone payments). See below.

According to this market report, the global Fabry drug market in 2021 was ~$2.1B.

If PRX-102 is approved, it would be the fourth Fabry treatment in the EU after Sanofi and Shire's ERT and Amicus' Galaford (an oral treatment) and the third in the US (Shire's ERT is not approved in the US).

In other words, PRX-102 would not be the first-in-class Fabry drug, and in terms of renal efficacy, it is certainly not the best-in-class Fabry drug (only a non-inferior ERT [to Fabrazyme] for adults, where the need is not as urgent as for young children diagnosed of Fabry Disease).

Furthermore, as stated recently, I believe that results from BRIGHT will not support the approval of a 4-week regime of PRX-102, which would have been an advantage over the 2-week regime of currently available ERTs.

Having said all this, I do understand that the short-term price action of small/micro biotech stocks are driven by many factors, e.g. speculative FOMO, penny stock/momentum trading, wider market volatility, besides the trial data or profitability of the company.

In my opinion, for long-term investors, the most significant risk is that PRX-102's prospect may not be sufficiently strong to ensure a real (sustained) turn-around in this stock, as:

Regulatory approval, in the EU and/or in the US, is not a sure thing;
If approved, it is a late comer without superiority in renal efficacy to compete in the established Fabry drug market;
Studies/approval for pediatric use is very far away, if ever.

[Spideyboy]

CC once again up to her tricks.

Here is my response to her new SA article:

Hi CC, and there you go again, incorrectly interpreting data, confusing the untrained eye, promulgating a false narrative.

Claim 1: The change in endpoint was only mentioned as of the April 4th PR. FALSE

If you were actually properly following the company, you would have known that it was Already Stated on the PLX November Q3 2021 EARNINGS CALL that the endpoint had been changed from Superiority to Non-Inferiority.

Please see the transcript of the earning call: "So the manufacturing is part of it. We are now -- we agreed with FDA that they will review the two years data with an endpoint of non-inferiority. And we agreed with the FDA that we will add the one in four weeks data for the review."
https://seekingalpha.com/article/4469602-protalix-biotherapeutics-inc-plx-ceo-dror-bashan-on-q3-2021-results-earnings-call-transcript

Also you can hear the CEO clearly say this if you listened to the webcast of the call available on the company's website. At minute 12:40.
https://viavid.webcasts.com/viewer/event.jsp?ei=1509878&tp_key=84fdbd0be8


Claim 2: ADA and neutralising measurements are essentially the same between PRX-102 and Fabrazyme. FALSE

You point out that the ADA+ve and neutralising antibody measurements are essentially the same between PRX-102 and Fabrazyme. However your comparative number "17 out of 18 ADA-positive-patients who showed neutralizing antibody activity, down to 7/11 vs. Fabrazyme's 7/8 to 6/6." are comparing on the ratio within each of the baseline and post-treatment groups and not the change between the baseline and post-treatment groups which is how you measure data in a trial you compare the change between what things we like before and then after, you should know this, I mean you're a DPhil and all right?

When looking at your presented data between the time points we see the following

Baseline - PLX: ADA+ 18, and 17 Neutralising. Post-24 months, 11 ADA+ and 7 neutralising. This means the drop in ADA+ patients Dropped by 38%, and the number of neutralising patients Dropped by 59%.

Baseline - Fabrazyme: ADA+ 8, and 7 neutralising. Post-24 months, ADA+ 6 and 6 neutralising. This means the drop in ADA+ patients Dropped by 25%, and the number of neutralising patients Dropped by 14%.

Thus while starting with the same baseline proportions, the drop in ADA+ and in Neutralising patients is staggeringly superior in the PRX-102 population compared to the Fabrazyme population.

As a DPhil, you clearly know this, but seems you choose to portray this data erroneously.


Claim 3: You seem to want to show the discontinuation in the respective groups as being of importance. Presenting this more favourably for Fabrazyme, (4% in Fabrazyme vs. 9.4% in PRX-102). But as someone with a DPhil would know that the discontinuation or drop-out is not as important as the reason for drop out, as drop out could have happened for any reason at all.

From the information in the BALANCE trials results PR, you seem to ignore to mention that of the 6 drop outs in the whole study population, of which 5 were in the PRX-102 arm, 1 was for withdrawal of consent, 2 for personal reasons, 1 unrelated adverse event and 1 was a treatment related adverse event. In the Fabrazyme group there was 1 for personal reasons too. Therefore your short portrayal of the discontinuation information of 4% vs 9.4% is misleading.

Misleading statement: You point out that Fabrazyme and Replagal are approved for pediatric populations while PRX-102 is not and has only performed trials to date in adults, as though this is some valid statement as per the potential of PRX-102.
OF COURSE this is the case, the product hasn't even been approved in the adult population yet with data just out. If this is such a valid statement, please show any information showing that Fabrazyme or Replagal were approved for the pediatric population before being approved in the adult population.

In the US, Fabryzyme was approved by accelerated approval in adults in April 2003, meanwhile the Fabrazyme pediatric study leading to FDA approval was only started in 2002 with primary completion date in 2005. https://clinicaltrials.gov/ct2/show/study/NCT00074958

Replagal was approved in the EU for adults in August 2001, and the study in Pediatric population only started in 2004 with Primary Completion data in 2011. https://clinicaltrials.gov/ct2/show/NCT00084084


The presented Topline BALANCE data clearly shows that the PRX-102 is non-inferior to Fabrazyme and that contrary to your put forward interpretation, the safety and immunogenicity data clearly strongly favours PRX-102. Thus as the potential 2nd ERT product on both the USA and EU markets, it has a good position to take considerable market share and associated revenues.

Best,
Spidey