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Thorn: Regarding AVA6000, doxorubicin’s 20–30-hour half-life is sufficient for effective tumor exposure, as it adequately delivers therapeutic effects without needing extension. This was known before the trial started. This was confirmed at an early stage in the trial when it was discovered that once cleaved dox behaved exactly the same as standard dox. However, for other payloads like exatecan in AVA6103, the short 9 hour half-life poses a challenge, limiting tumor exposure and efficacy. Avacta believes they’ve addressed this by extending exatecan’s half-life 6.5-fold to 60 hours through a novel linker in their second-generation pre|CISION platform, making AVA6103 viable. This half-life issue affects all companies using exatecan, but not doxorubicin, which has no such limitation. So is there a half life issue here? In short, there’s no half-life issue with AVA6000, but there is with exatecan-based payloads like AVA6103. Whether Avacta’s solution succeeds will be clearer when AVA6103 enters human trials in Q1 2026.

Avacta informed us that, when cleaved, AVA6000’s half-life matches that of standard doxorubicin, eliminating the need for extension, so I don’t see any issue here regarding half life

Regarding the pivot from STS, I trust CC’s explanation that the decision stems from updated facts. Specifically, the progression-free survival (PFS) for standard doxorubicin has improved from 6 months, as Dr. William Tap presented at Avacta’s Science Day, to 8 months, according to the latest Phase 3 trial data from last year. This makes AVA6000’s competitive landscape more challenging, and I’m pleased Avacta made the commercial decision to pursue targets with a higher likelihood of approval.

Avacta informed us that, when cleaved, AVA6000’s half-life matches that of standard doxorubicin, eliminating the need for extension so I don’t see any half life issue here.

Regarding the pivot from STS, I trust CC’s explanation that the decision stems from updated facts. Specifically, the progression-free survival (PFS) for standard doxorubicin has improved from 6 months, as Dr. William Tap presented at Avacta’s Science Day, to 8 months, according to the latest Phase 3 trial data from last year. This makes AVA6000’s competitive landscape more challenging, and I’m pleased Avacta made the commercial decision to pursue targets with a higher likelihood of approval.

Those shorts are increasingly underwater daily. They triggered the drop from £1.20 to £1 in early April. It’s still unclear why they chose to short amid the takeover news—very strange. Regardless, they’ll need to buy back, which will be spectacular.

I can only conclude from today’s RNS that the Alpha Board are optimistic a deal can be done with Corpay. We should remain cautious, as uncertainty persists about whether an offer will materialise and on what terms, but the extended dialogue keeps takeover speculation alive, which could sustain interest in Alpha’s stock. I have to say I wasn’t expecting this news today I thought the deal was gonna be dead

For those unfamiliar with Boehringer Ingelheim’s nerandomilast Phase 3 FIBRONEER-IPF trial, a concise summary is available at https://www.fiercebiotech.com/biotech/not-game-changing-boehringers-phase-3-lung-data-get-muted-response-analysts.

As already noted by others on here, the LYT-100 Phase 2b ELEVATE IPF trial data, released today, significantly outperforms nerandomilast in efficacy and tolerability. LYT-100 achieved an 80.9% treatment effect with a -32.8 mL FVC decline at 52 weeks, nearly halting disease progression, compared to nerandomilast’s 37.4% effect and -114.7 mL decline.

Out of interest I asked the same question to various AI's: 1) How much is LYT100 worth today 2) How much would LYT100 be worth if the phase 3 trial matches todays phase 2b data and gets FDA approval

Here are the results :

Grok: 1) $1.5B - $3B 2)$5B - $7B

Perplexity 1) $1B - $2.5B 2)$4.5B - $10B

ChatGPT 1) $200M - $500M 2)>$1B

Deepseek 1)$500M - $1.5B 2)$3-$6B

While these AI-generated valuations should be taken with a grain of salt, the exercise highlights something critical: PureTech’s stock is significantly undervalued as shown with even the most conservative of estimates. Also, lets not forget, Roche paid $8.3B for pirfenidone.

@jlovie, Im quite happy for the company to continue buying back shares whilst the price remains under fair value.

If PureTech Health's board issued an RNS tomorrow announcing the company was officially up for sale, the share price would likely nearly double overnight. Even in a fire sale, the asset value would certainly surpass £2 per share, a fact the market recognises. The reason PureTech’s current market valuation is significantly below this liquidation value lies in its status as a going concern. The distinction between operating as a going concern and liquidating the company profoundly impacts valuation. As a going concern, taking in to account the current share price, the market clearly views PureTech’s pipeline as weak, anticipating that it will burn through its cash reserves with little to show for it. This is the only explanation that I can come up with, that makes sense of the company’s strikingly low valuation.

Agreed Dallo. Its clear the Board are actively seeking out offers. This confirmation surely poses significant risk for the two disclosed short sellers. With the Boards clear intent these shorts must surely be forced to cover soon.

LYT100 is clearly going to be a very large and expensive phase 3 trial. Judging by what the CEO has to say below, I’m assuming its cost will likely exceed $100m as PRTC claim they don’t have the capital to fund it themselves. This seems odd to me considering the $340m cash balance. Anyway, looks like the plan for LYT100 is to spin it out as per the hub and spoke model.

“We are committed to advancing deupirfenidone while maintaining capital efficiency, in line with our proven strategy. Subject to feedback from the FDA with respect to trial design, as well as historical data from other Phase 3 IPF studies, we don't believe our current cash balance would be sufficient to fully fund a Phase 3 trial. We have therefore initiated discussions to explore a range of funding mechanisms-including a potential spin-out of the program into a new Founded Entity and accessing external equity financing, similar to our approach with Karuna and Seaport; project or royalty-based financing; and strategic partnerships - which may be used in combination, to support the program's continued development as we don't intend to fully fund a Phase 3 trial on our own. We will, however, continue to fund the program in the interim to maintain development momentum.”

The market is way over reacting to the disappointing read out from the adjunct schizophrenia trial for Cobenfy. The 7% Bristol Myers share price drop seems steep given that adjunctive therapy was a high-risk, high-reward trial with a historically low success rate, as acknowledged in BMY’s Q4 2024 earnings call:

Akash Tewari, Jefferies.

"Hey, thanks so much. So what's the risk around the adjunct schizophrenia trial for Cobenfy? Because we haven't seen a lot of companies run that specific trial. And if they have, they've often failed. So why wouldn't the probability of success for this trial be more like a 50-50 coin flip?"

Answer From Samit Hirawat (BMY)

"Sure. Thank you for the question. On the adjective schizophrenia, I remember where we started off and how patients are treated in the real world. So we obviously have developed the drug as a monotherapy, but these patients were primarily before they got onto the trial, we're receiving the D2 agonist and thereafter, there was a washout period, patients came on the drug and then, of course, the trial evaluated the primary endpoint in emerging one, two and three at a shorter window.But remember, merging four and five have now read out with a 52-week follow-up. Many of those patients obviously, are also taking concomitant medications in the background. So, and we've seen that efficacy continued to be maintained within, as we look towards the 52-week data point as well. So overall, from that perspective, we are confident on the overall safety profile that is emerging on that. And then, of course, from a blinded data perspective, the study has continued at this point. So now we are only a few months away from the readout for that trial. And, of course, on top of that, we'll look at ADAPT trials also reading out beginning at the back end of this year."

Lets not forget that Cobenfy’s primary schizophrenia approval remains intact, the adjunctive indication was a smaller market opportunity, and the drug’s pipeline for Alzheimer’s and other indications offers future potential. I guess the bears would counter me by saying the adjunctive failure reduces the TAM, impacting peack sales estimates. It also highlights the challenges of adjunctive studies, which have a high failure rate, and could raise concerns about Cobenfy’s broader efficacy profile.

Qube’s short on PureTech probably breaks even at 115p, so to make a 30% profit, they’d need to cover at 80p, valuing PureTech at just £190m, well below its £285m cash on January 1, 2025. Even if we assume a £40m burn in Q1, leaving current cash at £245m, Qube is essentially saying the company’s worth cash minus £55m (245-55 = 190). That’s a very gutsy bet, ignoring the risk of bids that could crush them. The risk-reward only makes sense if they’re nearly certain it’ll pay off which points to insider info and /or coordination which is fueling their confidence. If not why would you take a bet where your max win was only 30-35% but your downside could be 100% + ? Doens't make sense.

I also anticipate a slight boost to PureTech’s cash position from a Cobenfy milestone payment, as Royalty Pharma will likely owe them if the Phase 3 ADEPT trials for Alzheimer’s disease psychosis proves successful.

HarChris, it’s pretty obvious there’s a coordinated attack to tank PureTech’s share price. ActusRayPartners added to their short & Qube Research piled into a new short less than 24 hours after Nordic Capital’s bid on April 7, acting like they knew 100% the deal was dead on arrival. Yesterday’s price action dropping a further 12% suggests they either doubled down or new vultures jumped in, smelling blood. My gut says ActusRay’s either working with Nordic or got insider info on the bid’s fate. It wouldn’t shock me if potential bidders, maybe even Nordic, are engineering this trashing, with firms like Qube spotting the order book data and riding the wave to drive it lower. Market makers aren’t helping either, seeing the bearish flow, they’re positioning short, too. It all adds up to the share price demolition we’ve seen, from 138p to 103p in days. That’s my theory. Let’s be real: Nordic’s bid wasn’t a surprise, and with the stock now in the gutter, plenty of suitors are probably circling.

The vultures determined to trash the share price are still well and truly in control here still.

Dallo, The share price tanking 12.5% today suggests they’ve piled onto their shorts, maybe even new players jumping in. I hope you are right and they get burned tomorrow. From my vantage point, this reeks of a coordinated attack. Actusray’s short before Nordic’s April 7 bid was timed to perfection, did they get a tip the offer was a lowball? Nordic bailed them out fast, issuing an RNS just an hour later saying no bid, almost too convenient. Actusray was so sure the deal was DOA they upped their short to 0.60% the next day, again this reeks of insider knowledge. April 8—stage set. Were Qube in on it too, or did they just pounce on the bid collapse? As a quant firm, Qube’s algorithms feast on market data sensing weakness, they slammed in with 0.65% that same day. We will see tomorrow which other vultures have been trying to trash PureTech.

I can only assume that Actus and Qube know something we don't. Logic would tell you that shorting a stock when there is confirmed interest to buy the company is pretty reckless. There are some dark forces at play here.

Agreed. I've got an order in at 101p. I really hope it gets filled

@Lesley50

I see significant upside potential for the company based on the following: 1) It holds $365 million in cash reserves. 2) It has no debt. 3) Milestone payments from Cobenfy could reach nearly $400 million, plus potential royalties from sales that could add hundreds of millions more. 4) The company boasts a top-tier pipeline of late-stage clinical assets, many of which have blockbuster potential.

That’s my take. However, if you believe Cobenfy is a flop and the pipeline is weak, I’d agree it’s not the best time to invest heavily, caution would be warranted in that case. In fact if that is your view you should not be invested at all and probably sell on any bounce.

I’m genuinely thrilled about these low prices, there’s something exciting about a bargain in the market. It’s moments like this that call to mind the wisdom of arguably the greatest investor of all time, Warren Buffett. In a 2017 CNBC interview, he put it simply: “If you liked it at 60, you ought to like it better at 50". Even more memorably, in his 1987 Berkshire Hathaway shareholder letter, he wrote, “We welcome market declines as an opportunity to increase ownership in great companies at better prices.” I’m taking Uncle Warren’s advice to heart and loading up down here. My future self is going to look back and thank me for this move!