Member Info for Bmhltd

Can’t remember which presentation it was in, but does anybody remember his explaining that during the upcoming solid tumour trials they intend to treat the patient with Bex first to prime the immune system, before giving them PD-L1 in combination?

Makes sense now we understand the mechanism of action in more depth, ie reducee the truncated secreted clever-1, allow t-cells to regain function before revving up the immune system with both approaches in the doublet. Sounds like a very rational approach from a mechanistic perspective.

I think what would be absolutely ideal from a development perspective for Faron would be to sign a bumper upfront $ deal in solid tumours, enough to finance the phase 3 Bexmab 2 study, which would retain the ownership of Bex in all of Heme for Faron. Not saying this is the most likely but that would be my ideal scenario, obviously if a buy out north of $5Bn doesn’t land prior to phase 3, as that to me would be the next best scenario which guarantees a mega buy out, all else being equal if the data plays out as expected…

You don’t need a control group to do basic math…

https://www.onclive.com/view/dr-daver-on-initial-efficacy-and-safety-data-with-bexmarilimab-plus-azacitidine-in-higher-risk-mds

✅ 6. Juno Therapeutics

• BTD Drug: JCAR017 (lisocabtagene maraleucel – CAR-T) for relapsed/refractory DLBCL

• BTD Date: December 2016

• Acquirer: Celgene

• Deal Size: $9 billion (January 2018)

• Comment: BTD for aggressive lymphoma added momentum. The broader CAR-T field was also heating up, and BTD helped validate early signals.

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🔍 Summary: Why BTD Matters in M&A

Breakthrough Therapy Designation:

• Signals compelling early clinical data

• Provides regulatory acceleration pathways

• Helps attract strategic interest before Phase 3

• Often tied to platform or first-in-class approaches

• Can significantly raise acquisition valuations, especially in oncology and rare diseases.

ESPECIALLY IN ONCOLOGY AND RARE DISEASES!

Those with Fast Track, Front runner, Orphan Drug Designation, effectively the whole sweep effectively setting the scene for a revolution in Hemotologic-Oncology. The area most in need of new treatments with applications above and beyond just Heme.

I cannot see how the FDA can reasonably refuse BTD for bexmarilimab in both r/r & FL HR MDS.

Looking good for Faron.

Confident a little more patience pays BIG here…!

Quite sure FARN investors will prefer ChatGPT on BTD:

Here are several notable examples where the FDA’s Breakthrough Therapy Designation (BTD) contributed to the acquisition of biotech companies—often acting as a strong value catalyst by signaling high regulatory priority, encouraging suitors, and validating clinical potential:

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✅ 1. Forty Seven Inc.

• BTD Drug: Magrolimab (anti-CD47 antibody) for MDS and AML

• BTD Date: September 2019 (MDS)

• Acquirer: Gilead Sciences

• Deal Size: $4.9 billion (March 2020)

• Comment: Magrolimab had received BTD for high-risk MDS and was in Phase 1b. Gilead saw potential in combining it with azacitidine. The BTD and first-in-class target (CD47) significantly boosted investor and buyer interest.

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✅ 2. Loxo Oncology

• BTD Drug: Larotrectinib (TRK inhibitor) for NTRK fusion-positive cancers

• BTD Date: July 2016

• Acquirer: Eli Lilly

• Deal Size: $8 billion (January 2019)

• Comment: Larotrectinib showed strong early data and was the first BTD drug developed specifically for a tumor-agnostic indication. The BTD was key in securing accelerated approval and contributed to a high valuation in the acquisition.

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✅ 3. Immunomedics

• BTD Drug: Sacituzumab govitecan (Trodelvy) for triple-negative breast cancer (TNBC)

• BTD Date: February 2016

• Acquirer: Gilead Sciences

• Deal Size: $21 billion (September 2020)

• Comment: The BTD helped accelerate approval and drove significant clinical and investor interest. Gilead acquired Immunomedics shortly after Trodelvy received accelerated approval based on Phase 2 data.

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✅ 4. Tizona Therapeutics (minority stake with acquisition option)

• BTD Drug: TTX-080 (anti-HLA-G antibody; immunotherapy) for cancer

• BTD Not disclosed publicly but the candidate was in preclinical/early clinical stages with strong immunotherapy rationale.

• Acquirer: Gilead Sciences (option to acquire remaining stake after $300M upfront in July 2020)

• Comment: While BTD was not publicly listed, the strategic investment reflected the type of immunotherapy target that often attracts early attention when fast-track/BTD is expected.

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✅ 5. Blueprint Medicines (Gavreto) — Roche partnership (option to acquire)

• BTD Drug: Pralsetinib (Gavreto) for RET fusion–positive NSCLC and medullary thyroid cancer

• BTD Date: May 2020 (NSCLC)

• Partner: Roche/Genentech

• Deal Type: Licensing deal with an option to acquire

• Deal Value: Up to $1.7 billion (August 2020)

• Comment: The BTD for RET fusion NSCLC and strong precision oncology positioning made Blueprint a desirable partner for Roche. Later, Blueprint Medicines was seen as an acquisition target.

⸻

✅ 6. Juno Therapeutics

• BTD Drug: JCAR017 (lisocabtagene maraleucel – CAR-T) for relapsed/refractory DLBCL

• BTD Date: December 2016

• Acquirer: Celgene

• Deal Size: $9 billion (January 2

FDA Breakthrough Therapy Designation (BTD) can significantly increase the likelihood of a biotech company attracting bids for acquisition or partnerships due to the expedited development pathway and potential for faster market entry. This designation signals to larger pharmaceutical companies that the drug is promising and may be a valuable addition to their pipeline.

Here's why and some examples:

Why BTD Leads to Increased Interest:

Faster Development:

BTD streamlines the regulatory process, potentially reducing the time it takes to get a drug to market.

Increased Approval Chances:

Drugs with BTD have a higher approval rate than those without the designation, making them more attractive to potential acquirers.

Reduced Risk:

The close collaboration with the FDA during the BTD process can help mitigate development risks and improve the chances of a successful outcome.

Market Advantage:

Early market entry can translate to significant revenue potential, making the drug a more valuable asset.

Competitive Edge:

BTD can create a competitive advantage in the market, attracting attention from larger companies seeking to expand their portfolios.

Examples:

Moderna:

While not a direct example of a company being acquired due to BTD, the success of Moderna's COVID-19 vaccine, which benefited from the expedited development pathway afforded by BTD, highlights the potential impact of this designation on a company's valuation and market presence.

Exelixis:

Similar to Moderna, Exelixis experienced a boost in their valuation after receiving BTD for some of their cancer therapies, attracting attention from larger pharmaceutical companies seeking to acquire or partner with them, according to LevelFields AI.

Other Examples:

Many other biotech companies have seen increased interest from larger pharmaceutical companies after receiving BTD, leading to potential acquisitions, partnerships, or licensing deals.

In essence, BTD is a strong signal that a biotech company has a promising drug candidate with a high probability of success, making it an attractive target for larger companies seeking to expand their pipelines and market share, according to Parexel.

To obtain a Breakthrough Therapy (BTD) designation from the FDA, a drug sponsor must submit a request demonstrating that the drug is intended to treat a serious condition and that preliminary clinical evidence indicates it may offer a substantial improvement over available therapies. This request should ideally be submitted no later than the end-of-phase-2 meetings.

Key Requirements and Guidance:

Serious Condition:

The drug must target a disease or condition with significant morbidity or mortality.

Substantial Improvement:

Early clinical data should suggest that the drug demonstrates a substantial improvement on a clinically significant endpoint compared to existing treatments.

Preliminary Clinical Evidence:

This is crucial, as it indicates the drug's potential to significantly improve patient outcomes, even with limited data.

Address Unmet Medical Need:

The drug should address an area where existing therapies are limited or ineffective.

Timing:

While it's best to apply early in development, BTD can be valuable at any stage.

Submission Content:

The request should include information about the drug, the proposed indication, regulatory history, how it meets the criteria, and the type of marketing submission planned, according to the FDA.

FDA Response:

The FDA aims to respond to BTD requests within 60 days of receipt.

Important Considerations:

The BTD is granted for a specific drug-indication pairing.

The program aims to accelerate the development and review process.

BTD can lead to more frequent interactions with the FDA and streamlined development programs, according to Parexel.

Agree on that Wolfi, although I don’t think it should be feared either, and sometimes we need to roll the dice if fair offers for partnering are not forthcoming which I highly doubt.

Wrt director dealing, As long as there has been no firm offer, or exact $ figures on any form of deal been finalised, directors are able to trade shares, given it is public knowledge they intend to partner on the phase 3 development of Bexmarilimab.

My take is, Faron have been clear to other companies looking at making deals with Faron that they will await the EOP2 meeting with the FDA before they will discuss firm numbers so they know what the cost & size of the pivotal trial will be, the AA approval pathway, if Front Runner is confirmed, plus Faron will know there is a very good chance of BTD designation in, at minimum, the r/r population.

Given these crucial factors, it is entirely logical Faron are holding off on discussing figures, until they & potential partners know exactly what they are dealing with wrt likely costs of the trial, first approvals & full approval timelines, FDA recognition confirmation within the AA / front runner / BTD development frameworks & the value-add of these expected positive developments.

I believe the likelihood of these significant value adding events (confirmation of favourable AA pathway in r/r & FL) are likely & the trial size & timeline in the FL discussed at the Bexmab Data are fair and reasonable in terms of trial size (N) with the only factor Faron leaving out, being the AA in r/r, which likely comes at the interim RR readout ie, the midpoint of the AA pathway for the FL population (c.84 patient).

Being none-presumptuous toward

The FDA’s guidance has served Faron well thus far.

Given the previous communications with the FDA, the FDA guidance for submitting for BTD designation and the competitive landscape following the Venetoclax / Verona failure, there is still a chance an early mover, who wishes to reasonably speculate on the outcomes of the FDA meeting, placing a firm bid for the company, which Faron would have to bring to shareholders, so long as it is credible, with or without a recommendation for acceptance.

To assume M&A is not possible due to the director buys doesn’t hold weight, and with BTD likely, by my reckoning, within the next 4-5 weeks and the EOP2 meeting being at a similar / same time point, it feels the likelihood is a deal of some form follows shortly after but an early mover cannot be ruled out…

Very exciting times for the company and investors… GLA.

2/2

💰 Commercial Impact: Riding the Checkpoint Wave

From a commercial perspective, PD‑1 and PD‑L1 inhibitors are the best-selling class of cancer drugs globally, generating more than $50 billion annually. Yet response rates remain modest in many tumor types, and resistance is widespread. By combining bexmarilimab with checkpoint inhibitors, Faron could unlock new efficacy in “cold” tumors or in patients who’ve progressed on monotherapy. The sClever‑1 pathway doesn’t compete—it completes the checkpoint inhibition puzzle.

Such positioning makes bexmarilimab a prime target for partnerships or acquisition by large pharma players looking to:

• Enhance their PD‑1/PD‑L1 franchise (Merck, BMS, Roche).

• Penetrate hematologic oncology with novel immuno-oncology mechanisms.

• De-risk development using biomarker-enriched trial designs.

⸻

🚀 Strategic Outlook: A Next-Gen Asset in the Making

With a novel mechanism, biomarker integration, systemic immune modulation, and validated clinical activity in difficult-to-treat populations, bexmarilimab is emerging as one of the most compelling next-generation immunotherapies in oncology.

It sits at the intersection of macrophage biology, T‑cell reinvigoration, and precision immunotherapy—exactly where the future of oncology is heading. And with the newly uncovered role of soluble Clever‑1, Faron has laid the groundwork not just for better outcomes, but smarter, more targeted treatment paradigms across solid and liquid tumors.

1/2

I asked ChatGPT to speak to the importance of yesterdays RNS and its implications from a scientific and commercial perspective:

🧬 Scientific Innovation: Unlocking the Role of Soluble Clever‑1

Faron’s latest discovery of a secreted, truncated form of Clever‑1 (sClever‑1) offers a transformative lens into how cancers escape immune detection. Unlike membrane-bound Clever‑1, which modulates macrophage behavior, sClever‑1 directly binds to activated T cells and prevents their full effector differentiation — effectively blunting immune responses from a distance. This systemic immunosuppressive mechanism provides a second, previously unrecognized checkpoint layer that explains why many patients fail to respond to PD‑1/PD‑L1 inhibitors.

Importantly, bexmarilimab has now been shown to reduce circulating levels of sClever‑1, reversing this immune paralysis and restoring T‑cell function. That positions it not just as a macrophage modulator, but as a dual-action immune rejuvenator—one that acts across both innate and adaptive arms.

⸻

🔬 Biomarker Potential: Patient Stratification & Predictive Insight

The identification of sClever‑1 as a circulating immunosuppressive protein introduces a compelling biomarker opportunity. As a measurable blood-based indicator, sClever‑1 could help:

• Predict resistance to existing checkpoint inhibitors, like PD‑1/PD‑L1 antibodies.

• Stratify patients for bexmarilimab-based therapies, selecting those with high sClever‑1 as ideal responders.

• Track pharmacodynamic responses, helping to optimize dosing and monitor real-time efficacy.

This biomarker advantage gives Faron a precision medicine angle—something that few immunotherapies can offer at this stage—and strengthens its position in both clinical trial design and regulatory engagement.

⸻

💉 Hematologic Oncology: Expanding Into a High-Need Arena

The implications in hematologic malignancies are equally profound. Myeloid cancers like MDS and AML are often resistant to immune checkpoint inhibitors due to a heavily suppressive microenvironment. Faron’s clinical data already shows deep, durable responses in relapsed/refractory MDS when bexmarilimab is combined with azacitidine—including marrow remissions and transplant eligibility in patients previously deemed untreatable.

The role of sClever‑1 in this space adds a new dimension. Since many myeloid cancers are characterized by dysfunctional innate immunity and poor T‑cell activation, blocking sClever‑1 may serve as a core strategy for immune reactivation. This makes bexmarilimab one of the only immunotherapies with validated activity in post-HMA MDS, and with a mechanistic rationale to expand into AML, CMML, and even lymphoid cancers with macrophage-driven biology.

Yes, more great science and the revelation that secreted clever 1 is implicated in immunosuppressive tumour micro environment with Bexmarilimab working by blocking the receptor and thus the sClever-1 allowing for a immunostimulatory TME and the restoration of the immune system.

Bodes very well for this being a very unique immunomodulatory target, in that preventing the secretion will allow the immune system such as T cells to again become functional restoring innate immunity and cancer killing.

It also offers a super-strong rationale for combining with PD-1’s such as Merck’s keytruda & Pfizer’s Bavencio, given that high levels of sClever-1 are associated with resistance to anti-PD-1 checkpoint inhibitors.

Finally it offers a patented target and rationale for using sClever-1 to dampen overactive immune systems such as that found in many autoimmune diseases.

Very positive and highlights the point at which bexmarilimab can interject and change the course of cancers and explains a lot of unanswered questions about how and why the immune system becomes immunosuppressive and the cascade of events such as inactivated T-cell and CD8 cells come to pass.

Bexmarilimab and clever-1 a truly exciting target which appears to treat disease closer to the source of the disorder, or at least prior to the secondary effects which allow cancers to thrive and immunity to fail.

Truly cutting edge science and sure to open up a whole new way of thinking about cancer, its treatment and perhaps autoimmune disorders too.

Well done Faron, outstanding science…

If we take just the r / r HR MDS USA only population, at a conservative 4000 patients, multiplied by 12 months at the Rytelo price, indicated by Ralph Hughes’ market research at CMD day of $25,000 per month x 12 ( Conservative given 13.4 months survival), that is 4000 x $300,000 = $1.2Bn USD, just for r/r population in the USA alone on an incidence based model, which is lower than a prevalence model which factors in existing patients, as opposed to new r/r patients per year and ignores the rest of the world.

As mentioned prior, the likelihood of Bexmarilimab ‘not working’ in earlier stage patients is, in my eyes, for the birds, given the conventional wisdom that a treatment that works given earlier = better results, longer treatment time, more revenue and opens up a market 3 times bigger on a very conservative basis again in the USA alone.

On a pharma industry takeover multiplier, at end of phase 2 of 4-6x sales, if we take the mid-case of 5 that equates to $6bn USD, in r/r and US alone.

This isn’t going to be a hard sell given the lack of alternative options on the market, that being zero, and such a rapidly deteriorating illness post-HMA failure, especially now Venetoclax is out of the picture post-Verona.

This also, again, only factors in r/r and US numbers alone, furthermore it offers no value for AML, other hemo malignancies, solid tumours or autoimmune diseases, which is a monster market where billions are paid for pre-clinical candidates.

Bexmab data presentation postulated 164 patients for AA in the FL, likely AA at the mid point for R/R so following Response Rate data at 82 patients and full approvals for FL following c.360 patients, exact numbers on June 2nd webcast via Petri Bono’s segment.

As Juho stated, the high value hemo-oncology market in MDS & AML is crying out for something new, and we have it, especially if you understand the mechanism of action of Bex and the broad clever 1 positive population in Hemo-oncology.

This isn’t entirely true nglb, there is a cap of 9.99% of the total value of the company HCM can hold / convert, so there is a floor as far as I can gather.

The way I see it, we have probably one more conversion at most before we get to the EOP3 meeting with the shares amortising at 2 monthly intervals, at which point I’m almost certain that the r/r population will receive breakthrough therapy designation and will have the full phase 3 protocol in hand to make a deal on, as Juho said at the CMD, phase 3 are big endeavours and the high likelihood is this will be partnered failing a significant cash infection from elsewhere. Given at CMD, there were offers of cash already on the table and we since have matured survival data which is the ultimate endpoint, a deal will most certainly be achievable.

Therefore, I expect one more conversion before we can either start paying in cash, have big pharma / FDA recognition through a deal / BTD designation and in my opinion, this could be the catalyst for a bid for the company given they have more patients doses than forty seven did, when Gilead bought it out for $4.9B, with survival data eclipsing current SOC considerably, which is where forty seven fell over from an approvals perspective. Furthermore, we are seeing responses in TP53, the hardest of all HR MDS and 3x survival data over and above the 3 months under SOC, while there may be a few more games along the way, the maximum shares I can see being converted at a €2 VWAP conversion price (worse case,imo), is around 416,000 shares before we see the validation by big pharma / FDA as mentioned above.

Therefore, given the size of the potential prize I don’t see how this goes the way Avacta has, which is heavily diluting at this level, and still no deal confirmed, and a worse cash position and not as advanced with a pivotal trial to be shortly outlined.

All my own opinion, I remain bullish, good luck all…

Folks selling down having come this far based on a rumour in a web chat.

Crikey.

Good luck to them…

Https://www.europeanbusinessreview.com/faron-pharmaceuticals-earns-spotlight-at-eha-2025-with-its-bexmarilimab-data/

Retrospective in some regards but highlights the opportunity nicely here for accellerated approvals and the platform potential of Bexmarilimab.

Nice one Wolfi, if I had the cash I would be adding that many too….

Literally buying all I can at the min… LOL!

Nice one Wolfi, great interview, and nice pad for mr Zeidan. I bet he owns a few Faron shares…

Santhi, my take is broader turmoil in equity markets following expected US involvement in Middle East and a stagflationary picture was painted by the Federal Reserve at last nights CB meeting; I personally believe there are some games being played with the SP while somebody takes a position, I cannot prove this but that’s my take, so a bit of a double whammy this morning, although seems to be recovering a little now.

Bexmarilimab opens up a whole new market with dire unmet need. I added 252 shares this morning amidst the drama. Couldn’t resist at £2.04. Good luck all…

NP

Think you may have forgotten to post the link there Luck, I’ve attached it below. Thanks, hadn’t seen this.

Yes it is a little confusing, the way to look at it is there are 3 components which make up ORR, which are predictive of overall survival in blood cancers where complete responses are rare, otherwise known as a surrogate endpoint to sometimes allow early approvals, but usually during trials which can take a lot longer for overall survival versus the standard of care.. Faron or Bex already has nicely maturing data, especially in the r/r population, on survival, which is eclipsing the otherwise available treatments which may be an alternative HMA, other than Azacitidine.

The 3 components forming ORR in the IWG 2023 criteria are: Complete Response (blasts and blood fully resolved); marrow complete response + some hemotological improvement; and the final one is partial response which has equal to or over 50% recovery in blasts and some recovery in bloods (hemo improvement).

Of note from Mika’s interview was TP53 survival was 9.4 months, which when compared to survival of around 3 months usually (taken from the table presented at Farons Bexmab update post ASCO) is absolutely game changing for that population, and really up’s our chances of seeing a statistically significant overall survival endpoint in the upcoming pivotal trials. When TP53 is stratified for and spread across the control group equally, Bex should really shine as it overcomes what many other treatments haven’t been able to and will weigh the control group down but lift the experimental group (Bex treated up) creating a very substantial improvement in the overall Bex group compared to standard of care plus placebo….

Mika mentions they are currently preparing for trials in the FL population…

Suspect negotiations are getting rather interesting…

https://youtu.be/fcXVbgOS7eg

🔥

Https://www.vjhemonc.com/video/lge0zu5wfuy-an-update-on-immune-checkpoint-inhibition-in-mds-aml-investigating-sabatolimab-and-bexmarilimab/

Currently discussing with regulators…….!!!!