Member Info for Luckenbach

…getting a drug approval in one indication opens a lot of locks and doors.

Could this even be the first Bex trial that would gain a drug approval? Could do it rather fast because so Clever-1 rich. Would derisk the share quite. a lot even though the market could be from some tens of millions up to few hundred million. The company would make a break even?

No news what so ever that it could have given further understanding. No reason for any promise of upcoming webinar tells me that they are confident and the future brightens as granted. Btw is there a reason why the sp (NAZ) should approach the 2€ level from both sides in a constrained manner?

Faron’s sp is doing rather well in today’s general turbulence in Europe.

Yeah, so many holidays indeed. Any significant news needs to respect all markets equally. One day or another anyway soon?

When I woke up this morning full with energy I thought it was Monday already. So tomorrow I would like to be wiser concerning the CFO’s maneuver either way in positive or negative. Negative would be no news at all. Positive would be a RNS concerning a partnering or a complete or partial buyout offering. Maybe maybe wishing too much but some news from the JPM conference would be nice.

At least JPMorgan is seeing renewed momentum in European M&A.

Summary (Copilot) of the Bloomberg article on JPMorgan & European M&A

JPMorgan says Europe’s mergers and acquisitions market is finally showing signs of revival after a long slowdown. According to senior executives, investor confidence has improved, financing conditions are easing, and many companies that postponed deals during the high‑rate environment are now preparing to move ahead.

Key points

• Deal activity is picking up across Europe as markets stabilize and CEOs regain confidence.

• JPMorgan expects a strong year for M&A, driven by pent‑up demand and improved credit markets.

• The bank is hiring more dealmakers across nearly all major European countries, anticipating higher transaction volumes.

• Executives note that private equity firms are returning, supported by better financing conditions and pressure to deploy capital.

• Sectors showing the most momentum include technology, healthcare, and industrials.

• JPMorgan frames the environment as the most constructive in several years, though geopolitical risks remain.

Overall tone

Optimistic but measured: the bank sees a clear upward trend, not a sudden boom, and is positioning itself to capture increased deal flow as Europe exits the worst of the slowdown.

…and don’t hesitate to express your opinions.

”Aren’t errors and misunderstandings themselves potentially useful. Incorrectness isn’t merely a mismatch with facts; it is an active, creative force in its own right. Even when something is wrong or untrue, it can still carry historical weight.”

In good or bad I guess … and so true with many innovations.

Howard, there is always a risk of error and misunderstanding whenever a person engages with any text or subject.

A precise interpretation of a text must be grounded in the assumption that misunderstanding is the default, and that understanding requires continuous intention and effort.

It has even been said that understanding is merely one subtype of misunderstanding. Maybe maybe has its own category.

Things may be developing much faster than expected. The shares he maybe bought before his tenure wouldn’t be a problem if a major occasion was probably seen coming somewhere more far in the future. After his start more details were disclosed and maybe things just started to develop even faster than expected. Maybe a major deal is about to happen « unexpectedly soon ». Maybe indicative offer is in discussions and initial due diligence has already indicated that it doesn’t look good that shares were bought maybe just before his tenure the first of December.

Alternatively he just got these shares as a sign up bonus but doesn’t want to own any shares? So he sold them as soon as he got them after holidays? Ok selling right now doesn’t look that good but we don’t know him as a person. There is characteristically in general difference between business controller type and financial controller type of CFOs how they approach matters.

A pick up from the Finnish board.

Poiju posted.

”Bex gains recognition. iScience, Cell press, Nov. 2025 (Journal Pre-proof)

https://www.cell.com/action/showPdf?pii=S2589-0042(25)02185-6

“One promising approach involves the blockade of common lymphatic endothelial and vascular endothelial receptor-1 (Clever-1)+ TAMs, a maneuver that can initiate adaptive immunity and upregulate the expression of IFN signals and CXCL10. Furthermore, eliminating Clever-1 has been demonstrated to enhance antigen presentation and augment the secretion of pro-inflammatory cytokines such as TNF-α, interleukin-12 (IL-12). … Notably, targeting this subcluster might yield particular efficacy in non-inflamed ‘cold’ tumors that lack pre-existing IFN infiltration. Moreover, FP-1305 (bexmarilimab), anti-Clever-1 antibody has shown favorable therapeutic efficacy in patients with advanced solid tumor.””

I think this per-proof article from November bodes well with this concept of Clever Cluster Options.

criticism

******–meier survival curves and censorship in mds patients

******–meier survival analysis can be misleading in mds patients due to how censoring, treatment variability, and patient heterogeneity are handled—or not handled—in published curves. this affects how realistically patients and clinicians interpret prognosis.

why ******–meier is challenging in mds

******–meier curves estimate survival over time, showing the proportion of patients alive at various time points after diagnosis or treatment. in mds, this method faces several complications:

• highly heterogeneous patient population: mds ranges from mild anemia to aggressive leukemia-like disease.

• variable treatment responses: hypomethylating agents, for example, work well for some but not others.

• censoring can obscure meaningful differences: if a patient switches treatment, dies from another cause, or is lost to follow-up, their data is censored—potentially making survival curves look more optimistic than reality.

specific censoring issues in mds

1. incomplete follow-up

• elderly patients often have multiple comorbidities, and death may not be directly due to mds.

• if cause of death is unclear or follow-up ends, data is censored.

2. treatment crossover

• patients may switch from experimental to standard therapy or vice versa.

• this breaks the original treatment line, making survival curves less representative.

3. biological vs. clinical response

• a patient may show biological improvement (e.g., better blood counts) without clinical benefit (e.g., improved function or survival).

• if only biological response is reported, survival curves may appear better than they are.

4. unclear risk classification

• mds patients are stratified using systems like ipss-r.

• if risk groups are poorly defined or change over time, survival comparisons lose reliability.

what this means for patients and clinicians

• individual prognosis cannot be directly read from ******–meier curves.

• censoring may lead to overly optimistic or pessimistic interpretations.

• it’s crucial to consider treatment quality, life expectancy, and side effects—not just survival curves

…and then there is this thing called ai.

investor interpretation: ******–meier survival data for bexmarilimab

bexmarilimab is an investigational immunotherapy developed by faron pharmaceuticals, targeting the clever-1 receptor. its mechanism of action offers a novel approach to treating high-risk hematologic malignancies, particularly high-risk myelodysplastic syndromes (hr-mds) and acute myeloid leukemia (aml).

key takeaways from ******–meier curves

1. significant improvement in overall survival (os)

• in relapsed/refractory hr-mds patients, median os reached 13.4 months, compared to historical benchmarks of 5–6 months post-hma therapy.

• this suggests a clinically meaningful benefit that may support accelerated regulatory pathways.

2. efficacy in tp53-mutated subgroup

• tp53 mutations are associated with poor prognosis.

• bexmarilimab achieved orr of 78% and ccr of 44% in this subgroup—an unusually strong signal.

3. transition to curative therapy

• a notable proportion of patients (up to 35%) proceeded to stem cell transplantation following treatment.

• this indicates that bexmarilimab may alter the treatment trajectory, enabling curative options.

4. censoring and follow-up duration

• in several subgroups, median os has not yet been reached → censoring lifts the curve, but also reflects potential for durable benefit.

• this can reinforce investor confidence in long-term impact.

strategic messaging for investors

• bexmarilimab is not just a new drug—it’s a paradigm shift.

• ******–meier curves show potential to extend life, induce remission, and unlock curative pathways.

• while sample sizes are modest, the signals are strong and consistent, especially in hard-to-treat populations.

• censoring does not weaken the story—it amplifies the promise, as survival continues beyond current observation.

disclaimer, it’s ai, don’t trust it blindly!

Musk, Ellison and Bezos are visionary leaders who have been working on to realize their dreams like space flights. Then they have managers for their operations and specialists making it happen safely. Once they have the rockets on the launch pads people start gathering around having the biggest on wisdom what can go wrong.

Markku and Sirpa have been visionaries and Juho and Maija are in the management taking care that things do happen with the help of specialists like Bono, Kontro, Zeidan, Daver, SAB and many many other dr and PHd at the unis and sites. And now when something is expected to happen people start gathering around their pads having the biggest wisdom to criticize what could go wrong.

Just wanted to separate my previous post apart from BMS chain, because this doesn’t not have to be bound to BMS only or at all.

Cluster-Centric Drug Development: Unlocking the Full Value of Patented Therapies with Clever Cluster Options.

Executive Summary

Traditional oncology drug development is siloed by organ-specific indications. But solid tumors increasingly reveal shared biological mechanisms across tissue types. This shift enables a new model: cluster-centric development, where drugs are tested and deployed based on mechanistic clusters — defined by biomarkers, pathways, and immune escape features — rather than anatomical origin.

This model transforms how patented therapies like Bexmarilimab (Bex) can be developed, monetized, and scaled.

Scientific Cornerstone: Mechanism Over Organ

• Solid tumors are converging around shared immunological and molecular features.

• Bex targets Clever-1, a macrophage-associated immune checkpoint — relevant across multiple tumor types.

• Instead of pursuing one organ at a time, we focus on clusters of biological traits where Bex is mechanistically active.

AI-Powered Cluster Discovery

• Use AI to simulate, identify, and validate clusters of biomarkers and pathways where Bex is likely to be effective.

• Each cluster becomes a modular trial hypothesis, independent of tumor origin.

• This enables basket trials, tumor-agnostic approvals, and faster clinical validation.

Commercial Cornerstone: Option-Based Licensing

• Faron (or any patent holder) retains IP and cluster definitions.

• Big pharma partners license “cluster options” — the right to test Bex in a specific mechanistic cluster.

• Partners fund trials; Faron earns upfront fees, milestone payments, and royalties.

• This creates a new asset class: cluster-based trial rights.

Strategic Advantages

Efficiency: Reduces redundant organ-specific trials

Scalability: Enables parallel development across multiple clusters

Creativity with Focus: Encourages exploration while staying mechanistically grounded

Risk Sharing: De-risks early-stage biotech by outsourcing trial costs

IP Leverage: Maximizes value of existing patents without dilution

Vision

This model redefines drug development for the era of precision oncology. It empowers small biotechs to punch above their weight, and gives big pharma a plug-and-play mechanism to explore promising therapies across diverse indications — all while staying focused, efficient, and scientifically credible.

Developed my previous post a bit further:

Cluster-Centric Drug Development: Unlocking the Full Value of Patented Therapies

Executive Summary

Traditional oncology drug development is siloed by organ-specific indications. But solid tumors increasingly reveal shared biological mechanisms across tissue types. This shift enables a new model: cluster-centric development, where drugs are tested and deployed based on mechanistic clusters — defined by biomarkers, pathways, and immune escape features — rather than anatomical origin.

This model transforms how patented therapies like Bexmarilimab (Bex) can be developed, monetized, and scaled.

Scientific Cornerstone: Mechanism Over Organ

• Solid tumors are converging around shared immunological and molecular features.

• Bex targets Clever-1, a macrophage-associated immune checkpoint — relevant across multiple tumor types.

• Instead of pursuing one organ at a time, we focus on clusters of biological traits where Bex is mechanistically active.

AI-Powered Cluster Discovery

• Use AI to simulate, identify, and validate clusters of biomarkers and pathways where Bex is likely to be effective.

• Each cluster becomes a modular trial hypothesis, independent of tumor origin.

• This enables basket trials, tumor-agnostic approvals, and faster clinical validation.

Commercial Cornerstone: Option-Based Licensing

• Faron (or any patent holder) retains IP and cluster definitions.

• Big pharma partners license “cluster options” — the right to test Bex in a specific mechanistic cluster.

• Partners fund trials; Faron earns upfront fees, milestone payments, and royalties.

• This creates a new asset class: cluster-based trial rights.

Strategic Advantages

Efficiency: Reduces redundant organ-specific trials

Scalability: Enables parallel development across multiple clusters

Creativity with Focus: Encourages exploration while staying mechanistically grounded

Risk Sharing: De-risks early-stage biotech by outsourcing trial costs

IP Leverage: Maximizes value of existing patents without dilution

Vision

This model redefines drug development for the era of precision oncology. It empowers small biotechs to punch above their weight, and gives big pharma a plug-and-play mechanism to explore promising therapies across diverse indications — all while staying focused, efficient, and scientifically credible.

Let’s make it 6b in cash now for hema indications including additionally preferred partner options for solid indications each according to the cluster of endpoint/pathway/biomarkers/mechanism.

Bhmtl and itsallames, are you aligning? That’s almost collective intelligence in relation to BMS and Faron? Stifel 2025 Global Healthcare Conference next week! 5b? for hematology indications? In cash? Now? Have to sleep it over.

My rationale is that if the lower dose of bexmarilimab (1 mg/kg) demonstrates clinical benefit without corresponding biomarker activation or pathway engagement—while the higher dose (3 mg/kg) shows both—it raises a fundamental question: is the presumed mechanism of action valid? In such a case, the lower dose may act as a ‘clever placebo’—clinically active, yet mechanistically silent—challenging the rationale behind the drug’s development.

However nothing indicates that the outcome of clinical trials would turn out to such a situation. Thus it would be a kind of a contrapositive proof that Bex is on the right track when lower doses would show mechanical activity and not only accidentally clinical activity.

Bmhltd, I understand the need to see what is the smallest dosing that works. In case aza+bex1 would be weaker than aza+bex3 in all endpoints then of course the phase 3 would continue with 3mg/kg. No problem with having partners.

My point earlier here was (now in other way around) if both dosing levels would show up positively at all endpoints and biomarkers, it would be proven that Bex works.

If aza+bex1 would be about as good as aza+bex3 and better than aza alone and meeting endpoint like OS, surrogate endpoints and biomarkers, Bex could be approved later with 1mg/kg.

If aza+bex1 would be as good as aza+bex3 in OS (obviously no that kind of a data available at that point for decision making) but significantly weaker in binding clever-1, obviously as expected mainly because of an insufficient amount of Bex for saturating all or as many as 3mg/kg would bind clever-1 receptors, we could ask if we (I) understand all the pathways enough. Alternatively even a smaller amount of Bex would induce sufficient amounts of T cells to fight the disease. But if aza+bex1 would miss other endpoints and biomarkers it would mean there were no use for the expected logic of Bex, meaning bex3 would be as meaningless/meaningful as placebo (here bex1 that I wanted to call as clever placebo).

Quite absurd presentation above. My logic here says that basically both dosing 1 and 3 could be chosen to continue but 3mg/kg would have better odds for making the whole process through successfully.

Yes, now I am even more confused than any of you. All this without AI. A wiser could have ask this from AI.

Since the FDA guidance was announced concerning the optimizing of the dosing (1mg/kg and 3mg/kg) in the beginning of the pivotal phase. That’s been understood as a requirement of the Project Optimus. While it was not first clear to me that it is required because the 1mg/kg wasn’t not yet tested for the FL MDS and they need to find the lowest possible dosing.

So I tried to understand it and as not being a professional I got some thoughts like if that’s some kind of a technical protectionism delaying emerging new competition in the markets of the dominant BPs in the US?

The next thought was if the 1mg/kg dosing was some kind of a placebo against the 3kg/kg - a clever placebo? It could be used to see for example if there are significant differences in various measures even though both of them would meet the endpoints similarly or closely.

It would be then seen if the dosing level is sufficient for inducing the effects supposed to be the results of the explaining pathways. If there would be significant differences somewhere along the signaling pathways, enzymes missing what ever, but no significant difference in the endpoints, would it be then seen that Bex was not explaining the reached endpoint results in a plausible way? etc. etc.

Anyway there is this dual narrative for bexmarilimab’s activity that improves patient outcomes. The encouraging response rates in TP53-mutated HR-MDS, the transfusion independence demonstrating a tangible quality-of-life benefit and a better safety profile and hematopoietic recovery, cell level metabolism. So Bex fight the cancer and support the recovery of the patient’s own blood cell production. And what dosing level is enough for each or any of them or for all them?

Https://www.proactiveinvestors.co.uk/companies/news/1080875/faron-pharmaceuticals-ceo-on-encouraging-bexmab-trial-results-and-the-way-forward-1080875.html