Searching for high-tech pharmaceutical products: steady and boring or a roller coaster ride?

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Well, comparisons are always what they are. But the best head-to-head comparison I quickly got between these was that CR1, i.e., the 3y survival% for those in first remission, which was Sellas 47% vs Mendus 71%. Mendus’s patients are MRD+ (minimal residual disease remaining), Sellas’s perhaps not? I didn’t compare other differences… And I didn’t notice that Sellas is actually doing Ph3 in that CR2 group, so they are not direct competitors after all.

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But indeed, a good day for biotech. The US long-term interest rate fell today, perhaps that’s why? Hopefully it continues to fall :grin:

It’s worth checking out Mendus, it’s in the ‘speculative’ category. They claim that the vididencel vaccine increases T-cells that recognize precisely that WT1 marker (and a few others) also used by Sellas, meaning it presumably stimulates immunity against cancer.

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Thanks. I need to delve deeper into Mendus at some point. However, it seems it’s still maturing over time, as Phase 3 will take a long time with such long survival times…

I would think that the study is probably being done in the CR2 population precisely so that a statistically significant difference for comparison could be obtained faster, since the historical survival in the BAT group is only about half a year.

I don’t know how it would be done in practice, but I assume that if there is efficacy in the CR2 population, the indication will be tried to be expanded to CR1 as well (and why wouldn’t the vaccine work just as well in the first remission?)…

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Well, that’s what one would imagine. Research really takes ages, and we’ve certainly been waiting for a while now. The most impatient ones have already thrown in the towel long ago, myself included. I myself made significant percentage losses with Mendus a long time ago (the 10-month mOS benefit of the previous lead candidate remained statistically insignificant…), after which the stock price has dropped another -90%. I left a few shares as a reminder never to invest in early-stage biotech again.

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Alligator Bioscience comments on Henlius dosing first patient in the US in Phase 3 trial of HLX22 in gastric cancer – Alligator Bioscience

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Sellas delivered news today before the stock market opened. The SLS-009 Phase 2 study was successful (r/r AML), and the FDA advises proceeding to a Phase 3 study in first-line AML, which is planned to include approximately 80 randomized patients in two different cohorts: for patients who are unlikely to respond well based on their cytogenetic profile and those who do not respond to two cycles of aza+venetoclax.
It’s strange that the stock price isn’t moving anywhere (plus-minus a couple of percent) even though 9% of the shares have already changed hands, as far as I understand, during market hours, and I think another 4% changed hands in premarket. In the Stocktwits discussion, there are thoughts about this; one is probably that some hoped for direct Accelerated Approval news, and another is that the stock price is being deliberately pushed down by shorting, for example, because call options expire on Friday and sellers don’t want them to be exercised. I can’t say about these. A market capitalization of 200 MUSD is probably not unreasonable if there is faith in positive GPS Phase 3 results within a few months and another drug, SLS-009, going into Phase 3, which cannot be very expensive with 80 patients.

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I don’t know if this news belongs exactly to this thread, but I’ll put it here anyway. Yesterday I came across the Sonnet Bio case. What does it say about the market situation that small biotechs are being bought from the market and turned into crypto companies? :thinking:

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Well, exactly. Unimaginable amounts of speculative money are moving in the crypto “economy”. Maximum risk on offer. On the other hand, the post-GFC and post-Covid zero-interest rate era brought perhaps too many unhealthy companies, mainly at the business idea level, to the stock market, biotechs included. The pendulum movement is eternal, only the durations of the swings vary. At some point, that pendulum will inevitably swing back in the other direction…

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Hamlet BioPharma Holds Successful In Person Meeting with US FDA

The company is progressing to phase 3. No doubt about it. Surely a partner will be found for it too. A couple of consulting firms have been working on the matter, and the company has spoken about it in a positive tone.

Hamlet BioPharma Holds Successful In Person Meeting with US FDA

The stock price has only started reacting to this this week.

The cash is presumably already running low and will probably run out in August-September, so news about a cash replenishment should have already come unless negotiations with a partner are already very advanced. At least this is what the market now seems to think, that news about partnering will be received in August?

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Self-funded Phase 3 (cancer drug) is also still possible, and the higher the share price, the smaller the dilution. In December, the company made a direct offering during negotiations, and it can happen again, meaning it needs to show that it has the ability to raise money if a pharmaceutical giant, e.g., Pfizer, tries to extort it with delaying tactics.

However, from the CEO’s confidence, it can be inferred that negotiations are very far along. I see two key problems with the deal: that the substance acts as a general medicine for dozens of cancer diseases, and that the main owner wants the drug to be widely available, not just for the richest, i.e., what will be the selling price of the concoction. Oh, and a third problem might be that the company cannot be bought out; when the main owner dies, a foundation is formed, as I recall reading.

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There will certainly not be a rights issue - it would have already happened. A slow process. A directed issue might come, but a licensing agreement and a signing fee are more likely. Hamlet might have unofficial subscription promises for a directed issue as a backup plan in case the signing fee is delayed. Now, it seems, the finalization of the Phase 3 research plan is underway, which affects its costs and the figures in the licensing agreement.

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Not necessarily. Lately, it has been common to delay decisions for a very long time and then operate with a bridge loan until the money from the rights issue is received.

The markets also don’t know what will happen, so the price will likely move strongly in one direction or the other once the matter becomes clear.

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Directed issue, 10% dilution, I can’t find a better link right now, the company is updating its pages slowly:

“The proposed issue gives us an initial capital injection of SEK 30 million with the possibility of an additional SEK 110 million. We are humbly grateful for the trust in the company and will continue to use our capital efficiently for the optimal development and commercialization of our drugs. In parallel, we continue dialogues with several actors about potential collaborations and partnerships that can accelerate the projects”*, comments Catharina Svanborg, CEO."

30 SEK is 2.67 million euros.

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I haven’t found any previous mention of Biomea Fusion (BMEA) on the forum, so👇🏼

I bought the first batch today, and the stock is still in a completely speculative phase.

An orally administered Diabetes medication is under development for type 2 diabetics whose insulin production is significantly or completely impaired.

Results observed in Phase II studies: successful reduction of long-term HbA1c blood sugar levels by -1.5%, and what makes it special is that HbA1c continued to decrease even after treatment.

The initiation/increase of insulin production also persisted months after the treatment ended.

This suggests that the drug would not only be for symptomatic treatment but rather a medication that improves the course of diabetes.

High expectations for Biomea Fusion, apart from Peter Lawson/Barclays’ analysis and a $3 price target.

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Swedish Pila Pharma announced today that it has raised 30 million SEK in a 293% oversubscribed issue.

The company’s undoubtedly most valuable asset is the patents for the TRPV1 antagonist acquired from Novo Nordisk some time ago.

The metabolic effects of TRPV1 were studied by former Novo Nordisk researcher Dorte X Gram, who is said to have played a significant role in the early research of semaglutide. Currently, the founder’s son is the CEO. TRPV has already been studied in overweight diabetics in a Phase I study, and a Phase 2a study is also underway, but now, with the new funding, the aim is to start preclinical studies purely in the obesity indication.

First, studies in overweight rats are next. If these look promising, clinical trials will follow. These are intended to be financed by warrants distributed in connection with the current issue. Whether Phase II could be started directly in the obesity indication based on previous results is still unclear, but it would undoubtedly accelerate market entry.

One new share comes with one warrant, which allows subscribing for two shares at a 30% discount, between 1.50 - 3 SEK, after the rat studies are completed early next year. The valuation is not absolutely high even at the upper end, so if things go well, financing should be secured.

After the issue, the number of shares is 42.5 million, which corresponds to a market capitalization of 149 MSEK at a share price of 3.5 SEK, of which approximately 25 million is cash.

However, this does not tell the whole story, as warrants could lead to an additional 31 million new shares. If these are subscribed, the number of shares will increase to 73.5 million.

In such early-stage drug development companies, money is usually lost, but perhaps not this time. Gubra and Zealand Pharma from Denmark have recently concluded lucrative partnership agreements for early-stage candidates. Perhaps Pila can also achieve this, as it offers something different compared to all the GLP-1 drugs currently under development. But first, promising results from Phase 2a and rat studies would be needed.

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@Clark_kent wrote in the Faron thread: “An effective + mild cancer drug is a rarity.” Oh, it made me feel so good when I thought of Hamlet BioPharma! Its efficacy has been demonstrated in placebo-controlled studies, and good results persist during longer treatment and follow-up. There are hardly any side effects.

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Are you following the company? Has there been any information about what kind of Hamlet Phase 3 is coming? Hamlet’s website is a bit confusing. The announcement about the results of the FDA meeting did not clarify the matter.

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Good results and guidance from Medpace and Thermo Fisher. Is the sector finally starting to recover…?

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Now that Hamlet has been mentioned in the thread again, I got a bit excited to dig up more information about its possible mechanisms of action. I believe it’s good to try and understand these mechanisms, as it affects how this molecule can be utilized against cancer. However, in my opinion, the descriptions of Hamlet’s mechanism of action on its own pages are very unclear and do not provide a proper picture of how the molecule achieves its cytotoxic effect against cancer. This post, by the way, doesn’t contain much related to the investment case.

That Hamlet Alpha1H molecule is based on a peptide derived from α-lactalbumin combined with oleate. The parent molecule for this compound is partially unfolded α-lactalbumin + oleate, i.e., HAMLET. α-lactalbumin is an enzyme that normally produces lactose in milk. Therefore, it’s difficult to understand why this molecule should be cytotoxic against cancer cells.

However, this article has well characterized HAMLET’s cytotoxic effect on cancer cells: Conserved features of cancer cells define their sensitivity to HAMLET-induced death; c-Myc and glycolysis | Oncogene. It appears to be largely related to the regulation of glycolysis.

\u003e “This study investigated the molecular basis of HAMLET sensitivity in cancer cells, using screening techniques to detect features of transcription, protein interaction and metabolism that alter survival after HAMLET exposure. We show that sensitivity to HAMLET is dependent on c-Myc and glycolysis and identified the glycolytic enzyme HK1 as a potential direct target of HAMLET. The results also indicated that HAMLET alters cancer cell metabolism and that it may disrupt glycolysis, which is altered in cancer cells due to the Warburg effect.”

The regulation of glycolysis could also be biologically related to the function of α-lactalbumin, as cellular glucose is needed in mammary gland cells for lactose production in milk (lactose is formed from glucose and galactose). Adding to this the fact that many cancers are dependent on glycolysis for energy production (see Warburg effect), the mechanism of Alpha1H begins to seem plausible.

To conclude, I’ll add a miscellaneous selection of other points that support this glycolysis inhibition mechanism. MYC activates almost all glycolysis-related genes and has been shown above to affect HAMLET’s effect. Hexokinase expression levels affect the effect of potassium ions in glucose metabolism (on Hamlet’s mechanism of action page, the dependence of Alpha1H-mediated cell death on potassium ion flux is presented). And finally, HAMLET also has an antibacterial effect, which is mediated through glycolysis inhibition.

So, glycolysis and the Warburg effect could potentially be behind this mechanism of action, whereby the sensitivity of different cancer types to glycolysis inhibition could be a decisive factor in which cancers Alpha1H can be utilized for.

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Hamlet: scientific article published in March 2025

Stock exchange release on this - Scientific Breakthrough in Mechanism of Action

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I read that article when you linked it last time, probably in Faron’s thread when Hamlet was mentioned, but in my opinion, the cancer cell specificity of that ER-mediated mechanism remained unclear based on that article.

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