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6.8 times more drug actually reaches the blood stream with SPT320 vs regular agomelatine. Thats impressive. You can give a much smaller dose and still hit the drug levels you need for it to work. Smaller dose means way less liver exposure, which should mean no more liver enzyme spikes, which should mean no more blood test monitoring. Suddenly you've got a viable product for the US market.

The 10 fold drop in PK variability is also worth paying attention to. With standard agomelatine, two people can take the same pill and one gets hammered with drug while the other barely registers any. This problem is sorted with Glyph

This is great news. The lymphatic bypass mechanism is working cleanly in humans. Seaport is now advancing SPT-320 into two parallel GAD studies: a Phase 2a examining sleep benefits and a Phase 2b designed to be registration-enabling.

For me, the more important read-through here is for the Glyph platform and, by extension, SPT-300. Today's data add another layer of clinical proof that Glyph delivers on its core promise of bypassing first-pass metabolism. Today's results should give incremental confidence that the platform mechanics are sound heading into that efficacy read. I expect the market will shrug off this material news as usual, but my confidence in the Glyph platform and with it the probability of success for both SPT300 & SPT320 has increased after this excellent news.

This is an absolute no brainer buy at current levels. You're getting a business compounding earnings at 10%+ with 35% margins, 99% cash conversion, and a 3% dividend yield. In addition to this your getting an easy 35-40% re-rating upside once the market realises it sold the most AI-defensible company in the index as if it were the most vulnerable. Time to back up the truck, opportunites like this come around very rarely.

To truly capitalize on those major inflection points, the board absolutely must avoid selling Gallop or Celea on the cheap. If PureTech ends up with less than 40% retained equity in either entity post-funding, I'll be seriously disappointed.

For context, a Phase 3 trial for LYT-100 (leveraging the efficient 505(b)(2) pathway, building on established pirfenidone data) could realistically cost around $150M, that's very reasonable for a late-stage asset in world wide trail with hundreds of patinets. (Compare to my largest holding, Abivax, which is running its Phase 3 ulcerative colitis programme for roughly $350M ).

As I mentioned yesterday: if it takes a modest $50–75M raise to have the required capital to self-fund the LYT-100 Phase 3 (instead of handing over huge equity chunks to funding partners Celea), then so be it. We all know the prize here is potentially multi-billion-dollar. Sacrificing a smallish dilution now to preserve meaningful ownership and control makes total sense strategically. The setup is too strong to give away cheaply. I pray the PRTC board dont screw this up.

Nice to get ODD but this stock aint moving until the Celea funding news is out. We have 3 potential major catalysts in H1 that should - if positive - finally begin the long overdue rerate on this stock:

1. Celea funding deal & 1st patient dosing in the p3 lyt100 trial

2. Gallop oncology - Final data read out & completion of the p1b trial in AML

3. Gallop funding deal

Until then, the painfully dull wait drags on. We just need a little more patience. 2027 & 2028 look set to deliver the real needle movers: exciting late stage trial data readouts that will really light a spark under the share price if positive. In the great scheme of things, thats not long to wait.

honestly, if puretech is struggling to secure an acceptable deal for lyt-100, they should run the phase 3 trial themselves instead of waiting around. the phase 2b was stellar. replicating that success in a larger global trial will likely reult in lyt100 becoming the new soc in a market worth in excess of $10b by 2030.

the streamlined 505(b)(2) pathway should significantly reduce costs and timelines compared to a full de novo nda. this cuts tens of millions off development expenses. it also allows reliance on lyt100s exisiting data which will help increase chances of approval. a phase 3 trial under this pathway for ipf might relaistically cost $150 - $200m. all resources should prioritize suppoting this programme plus the other two programmes rather than wasting resources on other projects.

if i were running the company, i'd redirect focus entirely to these high-conviction assets and retain as much equity/ownership as possible in each, even if it means a modest raise , say $50-75m at current levels. biotech investors thrive on calculated risk for outsized rewards: a successful lyt-100 hit with near-100% ownership could deliver well in excess of $5 billion in value which will far exceed the modest returns from diluted stakes in the hub-and-spoke model.

whilst the hub and spoke model is smart for capital efficiency and has delivered wins, the nature of it means only modest rewards when you get a winner rather than the gargantunan upside the comes from owning a blockbuster outright. just look at the share price, the market has spoken, it hates the hub and spoke model so why the hell dont the board ditch it for lyt100. it's frustrating to see what looks like excessive caution or "*****footing" when the assets are this exciting, cash is ample, and dilution at these levels would be quickly forgotten if lyt-100 succeeds and becomes a $5b+ asset.

puretech's board needs to get its head out of the sand: stop giving away the family silver through premature or suboptimal deals, embrace some real biotech risk, and fully back this programme themselves.

Excellent interview with Seaports chair Steve Paul

https://www.biocentury.com/article/658314/serendipity-drives-discovery-in-psychiatry-engineering-gets-it-across-the-line-says-steve-paul#cprtstatus=_cp_0!channel!AYTD4YgdmyBx

This continued sell off in Sage tells me that the barriers to entry in accounting software are fundamentally misunderstood by the market. This Anthropic Claude panic is simply wrong. AI doesnt distrupt incumbents in highly regulated, trust dependant markets - it entrenches them. Sage is a clear beneficiary of this reality, Im very confident about this. I've started buying here today and Ive also purchased a good slug of Intuit.

ELF Beauty delivered a strong Q3 FY2026 beat yesterday, but the read-across for Warpaint is cautious. While ELF's results confirm the affordable beauty segment remains structurally attractive, management did flag specific UK market weakness. The main driver of ELFs success was from Rhode (Hailey Biebers brand) but organic growth from the rest of ELfs business was only 2% which is obviously a significant slow down.

In the call the CFO explcitily called out the UK market weakness: "We're seeing weaker consumption in the UK, and we're cycling our largest international launch to date with Rossmann Germany... we're seeing a highly promotional environment that has remained the case throughout the holiday."

As W7L is trading on a single digit PE, significant negativity is already priced in. So as long as we land within the guided range tomorrow and management arent too negative about the year ahead i think we should move higher. However, if the numbers disappoint (missing guidance) combined with any further guidance cuts for FY26 then we should brace for another leg down as this market is ruthless. Also, ELFs commentry about the "highly promotional" nature of the UK cosmentics market means we might see a bit of margin compression which the market wont like.

Fingers crossed for tomorrow. Im praying for a beat + improved outlook guidance. This will obviously rerate this stock signficantly, but based on ELFs commentry from yesterday I think this will be unlikely. I really hope im wrong on this

Superb trading update. We should be up significantly on the back of that today. Great start to life as a PLC. Happy days

Meaningful rise here today. Looks like that IPO overhang might have finally cleared. Fingers crossed

The next major inflection point - and without doubt the most important near-term catalyst - is the external financings for Celea and Gallop. This is where Kevin Tang could play a pivotal role. Its unlikely that his involvement here is a passive bet, so he's likely to scrutinise the terms closely to protect (and maximize) his economic interest. This is the real test of execution. With Tang in the mix, the odds of shareholder-friendly outcomes feel meaningfully higher than they otherwise would.

Https://substack.com/inbox/post/183896625?r=50c78&utm_campaign=post&utm_medium=web&triedRedirect=true

Thanks, Dallo.

I completely agree — PRTC very much has the "for sale" sign hanging out. It's been a frustrating journey for shareholders, no doubt, but even if the assets end up being sold on the cheaper side, we should still see meaningful multiples from the current share price. Gallop Oncology alone covers the entire market cap based on the strength of the LYT-200 data. This asset will alone get more valubale - as will all the assets for that matter - as data matures so any prospective buyer better get their skates on.

Also, big thanks to Rockefeller for posting the interview with Gallop Oncology CEO Luba Greenwood. In it, she shared a truly moving patient story from the LYT-200 Phase 1b trial. She described a woman who enrolled with relapsed/refractory AML after multiple prior lines of treatment and had been given only months to live. Thanks to LYT-200, this patient achieved a deep complete remission and is now cancer-free. The patient sent Luba a heartfelt letter expressing her gratitude and shared that she’s back out on the golf course — fully reclaimed the normal life she thought was lost forever. These kinds of real-world outcomes are incredibly powerful, especially in such a tough disease setting. They bring the impressive clinical numbers to life and highlight just how transformative LYT200 might be for patients.

The H1 2026 Inflection Point: What We Need to See and Why the Odds Look Good:

To fully grasp the stakes, let’s be brutally clear on the baseline. For patients in this exact setting (post-VEN/HMA failure, with a median of 3 prior lines of therapy) the established survival benchmark is less than 2.5 months. That’s the grim reality we’re trying to change.

Now, look at our initial Phase 1b data for LYT-200 at the proposed Phase 2 dose: 13.2 months median Overall Survival. The comparator isn’t another drug; it’s the relentless clock of the disease itself. We are showing a more than five-fold improvement over the expected outcome. This isn’t a modest beat; it’s a potential revolution.

The upcoming H1 2026 final OS update is the major inflection point because Overall Survival will be the primary endpoint in any registrational trial. The question is: will this remarkable early signal hold?

All evidence suggests the odds are strongly in our favour. This isn't based on hope, but on the data's architecture:

1. The Transplant Bridge: 50% of complete responders proceeded to stem cell transplant. These are patients who, by historical standards, had almost no chance of ever reaching this curative intent. Transplant creates long-term survivors, which actively supports and extends a median OS signal. It’s hard data proving these remissions are deep and clinically meaningful.

2. The Clean Safety Profile: With no LYT-200-related serious adverse events, there’s no "toxicity toll" dragging the survival curve down unexpectedly

Therefore, the probability that the 13.2-month OS collapses back to the historical range of 2-6 months is very low. The logical, data-supported probability is that it holds or even improves as the data matures.

The Path Forward and the Scale of the Opportunity:

LYT-200 already has Fast Track and Orphan Drug designation. Gallop plans to engage regulators on a potentially registrational Phase 2 trial after the OS data matures in H1 2026.

• Market Size: The addressable patient population in 2nd/3rd line AML is significant (estimates of 5-10k patients/year in US/EU).

• Sales Potential: With an innovative oncology price point, this represents a $700M-$1B+ peak sales opportunity.

The Bottom Line:

Let’s be clear: the market’s non-reaction isn't a sober verdict. It’s a fundamental mispricing of what this data represents. We are sitting on a potential best-in-class therapy emerging from a Phase 1b with a clean shot at a registrational path.

When that final OS data locks in H1 2026 and the path to approval becomes undeniable, today’s valuation will look absurd. Our job is to see the signal through the noise and let this extraordinary data do the talking.

Im so bullish

2/2

I’ve spent the Christmas break deep-diving into Gallop’s LYT-200 data from ASH. I genuinely cannot believe how the market has ignored it. This wasn’t just good news, it was a potential paradigm shift for late-line AML that was completely dismissed. The share price is no higher now than before this incredible dataset. I’ve taken the time to write this post because I want to make sure, we’re all crystal clear on what we own. The market might be asleep, but we shouldn’t be.

Let’s cut through the noise. Here’s why the market’s reaction is a clear mispricing:

LYT-200 is targeting relapsed/refractory Acute Myeloid Leukemia (AML) and high-risk MDS. This is arguably one of the toughest settings in oncology. The trial population was heavily pre-treated (median 3 prior lines of therapy). 87.5% had already failed the standard venetoclax/HMA regimen. The company states clearly that in this specific setting, expected overall survival is less than 2.5 months. Against this bleak backdrop, the LYT-200 data is nothing short of stunning.

The Survival Signal is Transformative:

At the proposed Phase 2 dose (in combination with standard care), the initial median Overall Survival is 13.2 months. Let that sink in. That’s a more than five-fold improvement over the expected survival. This data is still maturing, with the final readout due in the first half of 2026. If this signal holds anywhere near this level, LYT-200 becomes a potential new standard of care.

The Transplant Data Proves It:

The most telling detail, which the market seems to have missed entirely, is what happened to patients who responded. The combined Complete Response (CR/CRi) rate at the Phase 2 dose was a robust 38%. Critically, 50% of those complete responders were able to proceed to a stem cell transplant. In late-line AML, bridging to transplant is the holy grail, it’s the only potential for a cure. In comparable studies, this rate is often in the low single digits % or zero. The fact that a meaningful number of patients in this cohort (who had exhausted other options) could reach transplant is extraordinary. It confirms these are deep, meaningful remissions and strongly suggests the 13.2-month OS figure is built on a foundation of long-term survivors.

Safety & Broad Applicability Add to the Bull Case:

Favourable Safety: No LYT-200-related serious adverse events or dose-limiting toxicities were reported in 101 patients. This clean profile is crucial for a drug meant for very sick patients. Mutation-Agnostic: Responses were seen across high-risk mutations (KRAS, NRAS, etc). This isn't a niche therapy for a small genetic subset; it has broad potential applicability across most AML patients.

1/2

Thorn. This is where you’re asking the data to do something it simply isn’t designed to do yet.

Yes, we know from Dr Tapp, if you can keep STS patients on drug longer, you should see improved PFS. But that signal does not emerge cleanly in an early Phase 1b study with small numbers, heterogeneous subtypes, mixed prior lines etc etc. PFS is a time-dependent endpoint, it only separates meaningfully once enough patients have stayed on treatment long enough and enough progression events have occurred.

What AVA6000 has already shown is the necessary precondition for longer PFS: patients can remain on anthracycline treatment beyond what standard dox safely allows. What it has not yet shown is a mature, statistically robust PFS separation, because that requires a larger, later-stage dataset. Absence of that signal at Phase 1b is not evidence of failure; it’s simply the reality of oncology trial sequencing. You’re effectively judging AVA6000 as if it’s already completed a randomised Phase 2/3 STS study, when it hasn’t. That’s not a criticism of the drug, it’s a mismatch between expectation and trial stage.

I think it’s important to recognise that if doxorubicin in STS is already close to its efficacy ceiling, then it’s inherently difficult for any modified version, including AVA6000, to clearly beat standard dox in a head-to-head trial. That doesn’t mean AVA6000 hasn’t worked; it means the bar in STS turned out to be much higher than many expected.

Avacta appears to have recognised this since i remember CC mentioning a recent Phase 3 STS trial where an experimental asset went head-to-head with doxorubicin and failed, largely because the doxorubicin arm delivered materially better PFS than historical benchmarks. That result raised the regulatory hurdle significantly. In that context, even if AVA6000 clearly improves safety, the risk of failing to show sufficient efficacy separation in STS becomes very real.

Against that backdrop, the strategic pivot toward SGC makes sense. Here we’re seeing clear biological activity, there is no established standard of care, and the historic PFS benchmark for pre-treated stage IV patients (3.5 months) is relatively low. If the mature Phase 1b dataset shows a meaningful improvement in PFS, that’s a credible and potentially registration-enabling pathway. I would absolutely take that outcome as it would represent proof that the precision-delivery platform works in the clinic.

From there, the real upside shifts to 6103. With a modern payload and a delivery profile designed for sustained tumour exposure, this is where expectations rightly move toward deeper responses and broader applicability. If that kind of data starts to land, interest won’t be limited to the asset alone, it will extend to the entire platform. At that stage, the value proposition becomes very different indeed, which is ultimately why many of us are invested here.

Icecool - Fair point. When I said STS efficacy hasn’t been “spectacular” I didn’t mean negative. Its just that we don’t yet have a mature Phase 1b dataset that clearly resets the bar versus historical doxorubicin. Early STS signals are encouraging but as you rightly highlight, PFS take time to read out, so silence at this stage shouldn’t be over-interpreted

Thornogson, I think we’re closer than it might seem. On the evidence so far, AVA6000 hasn’t shown it’s ready to walk into a broad head-to-head against standard doxorubicin in indications like STS and clearly win. I’m happy to agree with that. The bar there has turned out to be quite high.

Where we still differ is the explanation. You attribute that to the 45-minute half-life; I see that as an intuitive leap rather than something the data actually demonstrate. The drug shows biological activity, sustained tumour exposure and durability in settings like SGC, which argues against simple under-delivery. To me, the more likely explanation is that AVA6000 improves the therapeutic index of a drug that’s already near its efficacy ceiling, rather than being fundamentally held back by its PK. For this reason Im not expecting "holy grail" type miracles from AVA6000. So in many ways, I think we actually agree on the current position, even if we disagree on the diagnosis. FAP-EXd may well turn out to be the broader, more disruptive asset but that doesn't make AVA6000 a failure, I would say it was just a more limited niche outcome that many of us had hoped for.