Demonstrating the added value of BEX requires a significant increase in CR compared to AZA
CR% remains close to AZA’s level (17%) → difficult to demonstrate added value → risk that there are no grounds for further development.
If CR% exceeds 25–30% → it can be reasonably assumed that BEX has a biological and clinical effect → a strong argument for a Phase III study/commercialization.
The probability % of whether CR% will reach a sufficient level is impossible to estimate, or it’s probably pointless to speculate further as there is no data.
However, AZA’s own CR% is already 17%, so if AZA + BEX does not clearly exceed the 17% CR level, it cannot be reasonably argued that BEX brings added value → in that case, there are also no sufficient grounds for Phase III development or commercialization.
Trusting the results, ph3 will proceed. Cash reserves are 50M€ these days, and as ph2 concludes, there’s room to increase the focus on ph3 planning & preparation. MOS is probably sufficient, and CR should be clear within two months, so the trading window is excellent. I would assume that the partnering window closes, for example, if that CR is 30-40%. Then the probability of an acquisition and a merger is real, because drug approval is pending and dependent on the initiated ph3. Couldn’t Faron get ph3 started without a partnership agreement if there starts to be a credible doubt about bigger issues? A partnership agreement could even slightly hinder that… An amazing year ahead for this story..
It is now known from the first line that for the first five patients, the ORR was 100%. Their CR was 80%. Now the ORR for all first-line patients has come in, which is likely to increase, i.e., still maturing, at 76%. Was CR not yet reported for the aforementioned reasons?
The 76% suggests that the first-line cohort size is not 20 but some other number. 25 would be exactly right, but as @Johanne_s mentioned, 16 responses from 21 patients gives a fairly precise 76%.
With the support of statistics enthusiasts, earlier in the thread, Fisher’s exact test can be used.
We already have 4 CRs. How many are needed in total to be considered a statistically significant number compared to aza alone?
Aza’s response has been 16-18%, let’s use 17%. The Bex cohort is 21. Let’s test if a total of 8 CRs from 21 patients is sufficient. It is sufficient:
Four CRs were already present, so only four more are needed. 4/16 patients for these new ones is 25% (!). For the entire cohort, 38%. That would be a percentage that would already grant marketing authorization, if such a small group were used. We won’t. The cohort will grow, and through that, more statistical power will be gained. There will be more safety margin, even if chance were to sway the results in the wrong direction. Faron had already calculated the requirements for phase 3 earlier. Also, a CR+PR combination could be considered as a requirement for marketing authorizations.
Vino Pino, Jerej, Clark as a critical voice, and others, a user named Dubious wrote the following on another forum. Comments?
”Faron’s press release was confusing. The headline ”BEXMAB Phase II trial met its primary endpoint in treatment-resistant High Risk MDS” is difficult to interpret, when there are several primary endpoints, and no specific targets have been set for them (this is rarely done in Phase 2 unless it’s a controlled study). An ORR (overall response rate) of 76% for Frontline (first-line) HR MDS patients leaves much to speculation. In March, Blood journal published the Phase 1b results for venetoclax+aza in 1st line HR MDS treatment for HR MDS patients. CR and mCR responses were 80% (104 patients). ORR also includes partial responses, meaning in an indirect comparison, bexa+aza falls short of vene+aza responses. In vene+aza treatment, overall survival was remarkably long compared to those published with aza alone (approx. 2x). Venetoclax has had marketing authorization for AML treatment for years, and even in the bexmab study, there are patients in the r/r population who received this combination as first-line. AbbVie has an ongoing Ph3 study in 1L HR MDS and results are expected in September 2025.
As I understand it, the FDA requires bexa to undergo a randomized controlled Phase 3 study in the 1L HR MDS population, where AbbVie’s study is already well underway. Since venetoclax does not yet have an indication in MDS, aza alone may suffice for comparisons. In any case, the results will be compared to venetoclax, and the bar is likely high. Venetoclax is in tablet form, meaning it’s easier for the patient, with somewhat more side effects, but the combination was stated in the Blood publication as ”Overall, venetoclax plus azacitidine at the RP2D was well tolerated and had favorable outcomes.”
Patients targeted by bexa will therefore likely have a very effective and well-tolerated treatment option with marketing authorization already by 2026. In r/r patients, bexa-aza has indeed yielded good responses even after vene-aza failed as first-line, but if bexa’s use were limited to the r/r population, the commercial potential would be significantly lower than currently presented.”
” In a previous Phase II study with venetoclax in HR r/r MDS patients, the ORR was 52% (CR+CRi-33). It is difficult to compare patients between studies, and venetoclax dosing has been developed in MDS, but it is very possible that bexa brings clinical benefit to these patients. In 1st-line, the threshold for bexa rises if the VERONA study succeeds Blood’s March editorial on the topic.”
”After initially administering azacitidine and venetoclax similar to how the drugs are given to patients with AML, and realizing a 20% septic death rate, the investigators cut the venetoclax dosing schedule in half, to 14 days of a 28-day cycle, combined with 7-day azacitidine dosing. Among 107 patients enrolled on this schedule, the CR rate was 29.9%.”
So, 20% died due to the side effects of that combination, and when the dose was reduced, the CR was 29%.
The overall survival with Aza+Vene as first-line treatment was only 26 months, compared to 24 months with Aza alone.
I certainly wouldn’t take that Aza+Vene combination if I had HR-MDS. It might give an extra 2 months of life, but the risk of dying from side effects would be 20%, and what kind of life would that be under the influence of that poison? No thanks.
Bex is in a significantly better position regarding its safety and also its efficacy. We only know that in the first sample (5 patients), 80% achieved CR with Bex + Aza as first-line treatment. It will probably come down a bit with a larger sample, but one would think it would certainly outperform Vene + Aza in terms of efficacy and safety.
The Verona trial and venetoclax have been discussed many times on the forum.
They stopped the studies in R/r (relapsed/refractory). They are continuing in first-line because aza+vene (azacitidine + venetoclax) is approved in AML. They had to change the primary endpoints, no longer CR (complete remission) as primary, but overall survival. That’s probably why it’s taking so long… Even Docent Kontro and Prof. Zeidan have mentioned the withholding of results. Apparently, CR doesn’t look good.
That toxicity is a problem, and Kontro also mentioned that the venetoclax dose needs to be adjusted. From that toxicity, my suspicion arose that possibly sicker patients (read: older, with multiple comorbidities, more severe cases perhaps are more readily directed to Bex, poor condition DOES NOT mean bedridden patient😅). We’ll hear later if that’s true.
The FDA considers efficacy and OS (overall survival) in marketing authorizations, but toxicity issues are also important. Clinicians too. If, as Markku J. summarized, they can spend the rest of their lives “in intensive care” with venetoclax treatment. Perhaps that was an exaggeration, but partly true.
And also the fact that patients who failed venetoclax treatment have come to Bex treatment, so they don’t rule each other out. It could also happen the other way around.
Nonsense. You have misunderstood what you read. That concerned a cohort of 10 patients with whom the study began. ”Of 10 patients exposed to the venetoclax and azacitidine combination, 2 developed fatal sepsis, resulting in a study redesign” The dose was adjusted because of that, business as usual. The correct figures in the article are 0.9% mortality due to venetoclax adverse effects and 1.9% due to presumed AZA adverse effects. ”Only 1 death (0.9%) was considered to be because of a TEAE possibly related to venetoclax, and 2 deaths (1.9%) because of TEAEs possibly related to azacitidine.”
16 April 2025, A&B (HK) Company Ltd (“A&B ”) divested its entire shareholding of 3,559,893 ordinary shares representing approximately 3.40% of the Company’s issued share capital.
Now it seems the top 30 ownership is entirely local, with a few Brits, Swiss, and Swedes at a quick glance. A&B’s motive for divesting is ultimately quite logical; is there such a leverage mechanism behind other major owners?
The writer seems to be very well-informed, and I, for one, have nothing to counter that. The Verona trial will be completed by the end of the year, as will bexmab’s data, so then we will be wiser again. If the product gets marketing authorization, then pexx’s accelerated approval chances will indeed go to zero.
P.S. That Hong Kong pot was absorbed surprisingly easily directly into the market; I think Faron’s stock will now turn northeast with the power of small investors.
" Hong Kong investment company A&B, which was among the major owners of drug developer Faron Pharmaceuticals, has sold its entire stake in Faron. A&B owned about 3.4 percent of Faron".
“A&B originally invested in Faron in 2025 as part of a strategic agreement related to Traumakine, which was then a development target for Faron.”
-Was there a mistake there, or am I delusional?
EDIT: So, the truth is likely that the company invested in Faron, and in a different product, in 2015. So there was incorrect information in the article.
How do you think about that study design for Vene+Aza? In a randomized study, it’s obviously a clear case if Vene+Aza is more effective than Aza monotherapy. But why isn’t Bex+Aza acceptable if it proves to be better than Aza monotherapy?
One argument has been that marketing authorizations have not been granted for combination drugs before, so why are such Vene+Aza studies even conducted?
You are at the heart of the matter. When one delves into previous approvals in oncology and hemato-oncology, it becomes clear that it is very rare for an approval to come for a combination where one component has not been previously approved for anything. Venetoclax, however, has already been approved for AML.
But that is, of course, just a statistic. Situations must be looked at one at a time, but in my thoughts, that statistic reduces beks’ LoA%.
Expectation management, on the other hand, has been the kryptonite of Faron investors. When the CEO visited Inderes to praise the company shortly before the directed share issue, talking about this issue was a direct insult to all parties. When the issue was then made exactly as expected, there was strong reassurance that this was just interim financing, as the partnership deal worth hundreds of millions or even billions was just around the corner, and big pharmaceutical companies were practically rolling out the red carpet for Jalkanen to create a new revolutionary cancer drug for them.
Well, now a longer-term financing solution has been made for Faron, which strongly signals that no partnership deal is coming anytime soon, but still the prevailing idea seems to be that a Finnish small investor will trick the stupid procurement teams of pharmaceutical giants by buying Faron’s miracle drug from the stock market at a bargain price. Those professionals must be utterly stupid if they refuse to make a deal.
There’s a tremendous amount of detailed technical expertise and intricate skill in the thread, but that famous common sense doesn’t always seem to keep up. The atmosphere is like listening to Poland’s Markku’s stories on the Voxtur forum back in the day. The financing is only for a year, so next we’ll be waiting for a new share issue or convertible bond, which will probably come sometime in Q4 2025. If things go well, some weak deal might be concluded in the autumn, but before that, there will be tremendously stormy price movements both up and down.
