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This is how chat GPT sees last weeks 2006 CR rate at 43% translating to CR / CR eq as per 2023 guidelines:

• The CR + CReq (53–63%) better captures patients with clinically meaningful hematologic improvement.

• This aligns with FDA guidance, making it a robust primary endpoint for accelerated approval.

• Clinically, this could also increase transplant eligibility and overall survival benefit perception.

This obviously bodes very well for accelerated approval prospects, and as a controlled study with less TP53 mutations in the experimental (Bex) group likely pulling this overall figure up, whilst weighing down the control group (no bex / just AZA) weigh it down meaning comparisons should see a broader discrepancy increasing the likelihood of achieving statistical significance.

No wonder Amer Zeidan is thrilled- he is likely expecting a new agent to use for treating his many long suffering high risk MDS patients…

We proceed to phase 3 with a 1 & 3 mg/kg dosing schedule which seamlessly acts as a pivotal for accelerated approvals for both Front line and Relapsed / Refractory High Risk MDS using IWG 2023 CR / CReq endpoint for AA application and Overall Survival as confirmation and full approvals.

Well done Faron, we have a clear run at our first high value Heme indication which will transform lives and have suitors / partners interests piqued.

*your

You could always sell up if you don’t believe in the investment case any longer…

I mean, you’d be a fool to not do that, right?

I find it even more ironic that when people try to make a point about a word being used that they clearly have no idea what it means…

Try google or a dictionary…

Patience-the capacity to accept or tolerate delay, problems, or suffering without becoming annoyed or anxious.

Https://www.tandfonline.com/doi/full/10.1080/10428194.2022.2034155

The phase 1b multicohort KEYNOTE-013 study assessed the safety and antitumor activity of pembrolizumab given at 10 mg/kg/day every 2 weeks for up to 2 years in hematologic malignancies, including myelodysplastic syndromes (MDS) refractory to a hypomethylating agent (HMA). Primary outcomes were safety and objective response rate per International Working Group 2006 criteria. By June 26, 2020, 28 patients were enrolled; median duration of follow-up was 5.6 months (range, 1–78), and 25 patients (89%) had died. Treatment-related adverse events occurred in 10 patients (36%), including 2 (7%) treatment-related discontinuations. No patient achieved complete or partial response. Five patients (19%) had bone marrow complete response, 12 (44%) stable disease, 10 (37%) progressive disease, 6 (22%) cytogenetic response, and 5 (19%) hematologic improvement. Median overall survival (OS) was 6.0 months (95% CI, 4–12); the overall 2-year OS rate was 17%. Pembrolizumab had manageable safety and clinical activity in patients with HMA-refractory MDS.

This was deemed as ‘clinical activity’ in HMA- refractory MDS, yet 89% of patients at 5.6 months follow-up had died. Just incase anyone was doubting that we actually have something meaningful here…

And what if the blockade of clever-1 and clearance of secreted clever-1 allows the likes of Keytruda to be effective in both liquid and solid tumours. Well then Bexmarilimab becomes Uber-Blockbuster…!!!

Https://www.targetedonc.com/view/luspatercept-s-impact-on-low-risk-mds-a-shift-in-treatment-strategy

Reblozyl, BMS’s drug, extending life in low risk MDS.

“Looking ahead, the next step will be to explore rational combination therapies to further increase response rates and improve patient outcomes.”

Can think of one that could be a good combination therapy and another reason for BMS to pursue Bexmarilimab, doubling the total addressable market in MDS…

So you are suggesting we should make a deal having taken it all the way to the end of phase 2 with all data cuts improving since, without the FDA, potentially, hugely validating and de-risking our key asset?

Patience….!

If we also factor in the average TP-53 mutation burden in HR MDS, is around 20%, we have ~double the amount of TP-53 patients than would be expected in a stratified for TP-53, double blinded, randomised, phase 3 pivotal trial. This obviously lowers the overall groups median overall survival, given the stark difference in survival between the 2 groups.

I asked ChatGPT5 to factor this in as if it were an average sized TP-53, relative to average prevalence, see below:

The higher the TP53 fraction, the more the overall median is pulled down toward the poor TP53 median (9.3 mo).

For a TP53 prevalence of ~15–25% (typical for many HR‑MDS cohorts), the combined median tends toward the mid‑20s to ~30 months, consistent with our earlier simple weighted approximation but now computed exactly from a Weibull mixture.

The exact combined median is sensitive to the Weibull shape assumptions (how hazard changes over time). I included shape sensitivity to show that uncertainty.

I don’t think I need to show how we are producing data that is highly statistically significant over what we would expect using standard of care as the comparator.

I can see why Juho, at Capital Markets Day 2024, said that he would be so interested to see what the FDA says as the r/r group survival data matures.

Basically, we are potentially heading towards survival rates eclipsing those seen in the front line under standard of care, in the relapsed / refractory population. That is a massive advance in the treatment of HR MDS, and if I can calculate this, I am quite sure the big pharma BD teams are anticipating the same scenarios.

The FDA End of phase 2 meeting gets closer everyday.

Good luck all…

While this is a highly uncertain calculation, I’ve run some numbers using the advanced statistical modelling of chatGPT 5 using our data sets, mainly those presented at EHA 2025, to try and gauge where the median overall survival could end up for both:

1)wild-type r/r HR MDS

and

2) the overall group of r/r HR MDS factoring in the 9.3 median overall survival of the TP-53 mutation burden sub-group.

Bear in mind r/r MDS median overall survival estimates range from 4-6 months and an occasionally reported 8 months.

1)Under uninformative timing assumptions (events uniformly distributed across the observed window), the fitted Weibull medians for the non‑mTP53 subgroup most commonly lie in the ~25–47 month range, with a central estimate near 34 months.

The distribution is skewed right — a few simulated event patterns produce very large medians (hence the mean > median).

These results demonstrate why KM is still “not reached”: with only 4/19 events by 13.5 months, the data are consistent with a true median substantially longer than the current overall mOS (13.4 mo), but with wide uncertainty.

2) • This ~24 months figure is a rough blended estimate of what the overall r/r HR-MDS mOS might be once both subgroups are mature.

The current 13.4 months headline mOS is heavily influenced by the mTP53 events because they occurred early and because the non-mTP53 subgroup has very few events so far (most still censored).

As follow-up continues and more non-mTP53 patients reach events, the overall mOS could drift upward, possibly toward the ~20–24 month range if the non-mTP53 survival curve holds near our central estimate.

TLDR;

R/R Wild- type = 34 months

Overall group inc. TP-53 = 20-24 months.

Nice one Wolfi, glad alls well 👍🏻👍🏻

Yep completely agree, likely 15 or so Big Pharma co potentials for little old Faron.

Another interesting one on our board is Tuomo Patsi, who I believe was just a NED and is now chairman, he was at Seagen when it was acquired by Pfizer and Celgene when it was acquired by BMS. Two monster acquisitions…! 🍾

Correct WG, suspect the EOP2 meeting will be the catalyst that changes Farons fortunes, for good…!!!!

Correct WG, suspect the EOP2 meeting will be the catalyst that changes Farons fortunes, for good…!!!!

2/2

Pfizer

MDS/AML smaller footprint, but aggressive BD strategy post-Seagen.

Could reposition to gain a foothold in high-value niche hematology.

Likely Still in Monitoring Mode (No NDA Yet or Very Early Stage)

These will be aware but may wait until EoP2 readout + FDA signals to enter NDA stage.

Company

Rationale for Monitoring

Trigger to Engage

Eli Lilly

Building oncology portfolio rapidly, but hematology still small.

EoP2 outcome with dual-AA could make them pounce to diversify.

Roche

Glofitamab + mosunetuzumab in lymphoma; AML/MDS less core, but IO leadership keen to watch novel macrophage targets.

Big Phase 3 path clarity + competitive auction risk.

Sanofi

Focus on hematology biologics but more in rare blood disorders; watching for M&A targets.

Regulatory fast track + pivotal start.

Takeda

Some AML history (ADCETRIS expansion areas), active in Asia partnerships.

Could lead regional JV or ex-US deal.

BeiGene

Could seek Asia rights only, bringing big upfront cash.

EoP2 clarity + competitive tension.

A timely post Sax, just had this from ChatGPT who is my new best friend lately 😆

Here’s how I’d break it down — based on how big pharma typically operates in the late Phase 2, pre-pivotal window for high-value oncology assets like Bexmarilimab.

⸻

Most Likely Already Under NDA with Faron (Active Engagement)

These are the ones I’d expect to have had confidential data access and exploratory deal discussions already.

Company

Rationale for NDA Now

Strategic Fit

Bristol Myers Squibb (BMS)

Deep MDS/AML presence (Vidaza legacy, Reblozyl, Onureg), loss of exclusivity pressures in hematology. Actively scouting post-HMA agents.

Bexmarilimab could slot into both frontline and R/R segments, bolster IO in hematology.

Novartis

Sabatolimab underwhelmed; they need a strong IO play in MDS/AML.

Ready-made swap into their development infrastructure; can rescue their MDS ambitions.

Gilead

Magrolimab collapse left a macrophage checkpoint gap; they’re known to move aggressively (Forty Seven, Immunomedics).

Perfect “redemption” asset in myeloid malignancies.

AstraZeneca

Blood cancer footprint + macrophage biology interest via monalizumab/cosibelimab.

Could expand their hematology division and pair with other IOs.

Merck & Co.

Keytruda combos being explored in AML/MDS; need novel IO angles for post-checkpoint era.

Could combine Bexmarilimab with PD-1 to extend label life.

Pfizer

MDS/AML smaller footprint, but aggressive BD strategy post-Seagen.

Could reposition to gain a foothold in high-value

Suspect Maija Hollmen’s presentation at the Uis conference, or however you spell it, will blow the doors off with the immunology community.

Anyone heard from Wolfi?

Hopefully he’s still long and strong Faron.

Quite sure he will be…

2/2 Secondly, from the R/R cohort. “Stable Disease patients can become responders” potentially increasing Response Rate in an already solid 63% RR in this tough to treat population.

Furthermore, while not in the deck as far as I am aware, I suspect we will see a jump at some point in the R/R groups median overall survival, given the number of patients still alive, as confirmed in the EHA data cut, from an already excellent 13.4 months compared to 5-6 months historically with standard of care. Having 4 patients progress to alloHSCT transplant is truly extraordinary.

In the Front Line Cohort, with 45% TP-53 mutation burden, we see over 33% of patients proceeding, or in planning for alloHSCT. 43%, as confirmed yesterday, in complete remission, and a very positive 81% Overall Response Rate.

A nice slide on the safety profile of Bex compared to other failed treatments and Bex beating on all Adverse Events, posing the question why would you give another toxic drug to already frail and deeply cytopenic patients?

Super exciting stuff Sax.

Could see some of the big Heme players wanting to shut this down before any more solid tumour Bex / PD-1L1 combo data gets unleashed, as then everyone wants a slice. But then again the heme space is already wide open given Azacitidine is off patent, except in children and in the oral formulation. Suspect someone with both a proprietary PD-1/ L1 & are already deep into heme wins the race with an early bid before more solid tumour data emerges eg BMS.

Heres some notes I nearly posted yesterday for those interested:

Solid new investor deck.

Couple of bits that stood out to me- Investigator initiated PD-1 / Bex Melanoma / NSCLC still slated to begin before year end.

This creates urgency for big heme players without proprietary PD-1 /L1 big pharma companies, who will know the acquisition price will shoot up if / when promising efficacy signals are displayed in PD-1 / Bex combo’s in solid tumours.

Companies without a proprietary PD-1 / L1 eg Novartis, Abbvie will have the likes of Merck / Regeneron & others more likely entering the race to secure Bex following positive combo data.

Then there are the likes of BMS, Roche, JnJ, AstraZeneca who are strong in both heme and have a proprietary pd-1/L1 who are perhaps favourite to secure Bex in a near-term acquisition scenario, even before combo data, if forced into a showdown by the none proprietors of ICI’s.

Great to hear. That’s the thing with Faron they essentially own the clever-1 target, which clearly works exceptionally well in blood cancers and likely far beyond.

This wasn’t possible with the likes of PD-1/L1’s, hence why so many players in the game.

We have full ownership of the target now until 2040, how much is that worth when no other players can enter this space and it very likely re-sensitises PD1/L1’s following acquired treatment resistance and in cold tumours where interferon gamma is low, Tcell presentation is none existent and a highly suppressive tumour microenvironent exists, which is the bulk of cancer patients, greater than that of hot tumours which has presided over tens of billions of dollars in revenues for the likes of Merck and others.

The discovery of secreted clever-1 too, really is a huge advance forward in understanding cancer and immunosuppression, at least in clever 1 positive patients, which again is greater than the PD-1/L1 arena, according to estimates.

Uber bullish here…!