Silicon Investor - Biotech Valuation

[Damián] So it's as if the stocks were experiencing a kind of inflation, so many dilution...

Damián — 3/15/2026 9:21:59 AM

So it's as if the stocks were experiencing a kind of inflation, so many dilution and shareholders equals to 0 value to the stock.

Basically, too risky invest right?

[waitwatchwander] Shares outstanding is the issue here. How did it get that high? share.google ...

waitwatchwander — 3/15/2026 8:02:48 AM

Shares outstanding is the issue here. How did it get that high?

share.google

It looks like it's burned through a ton of money to get where it is today. I'd be taking a good look at it's balance sheet to see what of the assets are still viable.

share.google

[Damián] Elite Pharmaceuticals, Inc. Hello, I have heard from this company and it looks ...

Damián — 3/15/2026 6:11:57 AM

Elite Pharmaceuticals, Inc.

Hello, I have heard from this company and it looks too good to be true.

A guy was saying that this company has 140 million in annual income. This company only has 68 employees so they earn 2 million aprox per head. Also, I heard that they could be bought by Pfizer or some of the biopharma giants easily.

It is a pennystock.

Let me know what you think. I heard this all from internet and could be wrong.

Thanks.

[A.J. Mullen] First post of the year!? XENE up over 45% today on good results from their P...

A.J. Mullen — 3/9/2026 11:23:49 AM

First post of the year!? XENE up over 45% today on good results from their Phase III results for a drug, azetukalner, with a new mode of action against epilepsy seizures. Good efficacy, manageable side-effects, no titration, once-a-day pill.

[JamesK] Congrats to REGN on FOP investor.regeneron.com

JamesK — 9/17/2025 8:56:56 AM

[Ian@SI] …. And one last comment from me With no AI assistant help. Even if these fail...

Ian@SI — 8/5/2025 4:50:26 PM

…. And one last comment from me With no AI assistant help.

Even if these failed attempts do destroy the brain’s immune system, I suspect that most Alzheimer’s patients And their families would welcome any reduced time and suffering For the patient. Not exactly a cure that the FDA will ever approve it may be something that the Alzheimer’s patient would want if they only had sufficient awareness.

[Ian@SI] Here’s a quick response from Gemini to my first question on Tau tangle research....

Ian@SI — 8/5/2025 4:41:55 PM

Here’s a quick response from Gemini to my first question on Tau tangle research.

Attempts to develop drugs targeting tau tangles have been a significant part of Alzheimer's research, especially as the failures of amyloid-targeting drugs became more apparent. However, the path has been similarly challenging.

Attempts that have made it to Phase 2 or Phase 3:

* LMTM (Hydromethylthionine mesylate): This tau aggregation inhibitor developed by TauRx reached Phase 3 trials.
* Gosuranemab (BIIB092): A monoclonal antibody designed to clear tau from the brain, it advanced to Phase 2 trials.
* **Tilavonemab (ABBV-8E12): Another monoclonal antibody targeting tau, which also reached Phase 2 trials.
* Semorinemab (RO7109575): This antibody from Genentech and AC Immune made it to Phase 2.
* Tideglusib: A GSK-3ß inhibitor, which is an enzyme involved in tau phosphorylation, that went into Phase 2 trials.
* ACI-35: A vaccine targeting phosphorylated tau, which has been in Phase 2 trials.

It is difficult to provide a precise, up-to-the-minute number for all tau-specific trials as new studies are constantly being registered, initiated, or terminated. However, based on available data from scientific reviews and clinical trial registries, a number of tau-targeting drugs have reached late-stage development.
Failures between Phase 1 and Phase 3

The number of failed trials is substantial. A significant portion of the tau-targeting drugs that reached Phase 2 or 3 have ultimately failed to demonstrate clinical efficacy.

* Gosuranemab: Was terminated after a Phase 2 trial failed to show a benefit in slowing cognitive decline.
* Semorinemab: A Phase 2 trial for this drug failed to meet its primary efficacy endpoint.
* Tilavonemab: A Phase 2 trial for this drug was also stopped due to futility.
* LMTM: The Phase 3 trials for this drug failed to meet their primary endpoints.
* Tideglusib: Clinical trials were terminated after it failed to show a significant benefit.

These examples represent some of the most notable failures, but they are not exhaustive. Many other tau-related compounds, including various aggregation inhibitors, microtubule stabilizers, and other antibodies, have also been discontinued in earlier phases (Phase 1 or 2) due to a lack of efficacy, safety concerns, or futility. The experience with tau-targeting drugs is mirroring the amyloid story, where many promising candidates in preclinical studies have not translated into successful treatments for patients.

[Ian@SI] I also asked Gemini how rapid the researchers were migrating to different approa...

Ian@SI — 8/5/2025 4:21:56 PM

I also asked Gemini how rapid the researchers were migrating to different approaches to identifying a cause and solutions to the Alzheimer’s disease problem. Gemini answer follows.

The shift in Alzheimer's disease research from the dominant amyloid and tau hypotheses to a focus on pathogens is a significant and growing trend. It represents a fundamental re-evaluation of the disease's underlying causes, driven by the consistent failure of amyloid-targeting clinical trials.
Here's a breakdown of the significance of this migration of thought:

1. The Limitations of the Amyloid and Tau Hypotheses:
For decades, the "amyloid cascade hypothesis" has been the prevailing theory. It posits that the accumulation of amyloid-beta (Aß) plaques in the brain is the primary cause of Alzheimer's, leading to the formation of tau tangles, neurodegeneration, and cognitive decline. The vast majority of research and drug development has been based on this model.

However, the repeated failure of numerous clinical trials (including the 98 mentioned previously) to effectively treat or reverse the disease by clearing Aß and tau has cast serious doubt on this hypothesis. While some recent anti-amyloid drugs have shown a modest effect in slowing cognitive decline, they haven't been the "cure" that researchers hoped for. This has led many in the scientific community to believe that Aß and tau are not the root cause, but rather a downstream effect or even a protective response to a more fundamental problem.

2. The Rise of the Pathogen Hypothesis:
The "pathogen hypothesis" is gaining traction and offers a compelling alternative. This theory suggests that Alzheimer's is a response to an infection in the brain caused by various pathogens, including:
* Bacteria: Spirochetes, such as those that cause Lyme disease, and bacteria involved in gum disease (Porphyromonas gingivalis) have been found in the brains of Alzheimer's patients.
* Viruses: Herpes viruses, particularly HSV-1 (which causes cold sores), have been linked to Alzheimer's pathology.
* Fungi and Parasites: There is also a growing body of evidence linking other microbes to the disease.
The pathogen hypothesis re-frames the role of Aß. Instead of being the primary villain, Aß is seen as an antimicrobial peptide—part of the brain's innate immune system that clumps around invading pathogens to neutralize them. The plaques, in this view, are essentially graveyards of dead microbes and the Aß proteins that encased them. Over time, a chronic, low-grade infection leads to a persistent immune response, causing inflammation, and ultimately, the neurodegeneration characteristic of Alzheimer's.

3. The Significance of the Shift:
This change in perspective is significant for several reasons:

* New Therapeutic Avenues: It opens up entirely new avenues for treatment. Instead of just targeting Aß and tau, researchers can now focus on developing antimicrobial and anti-inflammatory drugs. Clinical trials are beginning to test whether antibiotics, antivirals, and other anti-pathogenic therapies can slow or prevent the disease.

* Reframing the Disease: The pathogen hypothesis offers a more comprehensive explanation for the complex pathology of Alzheimer's. It accounts for the presence of Aß and tau, the role of inflammation, and the disease's association with genetic risk factors (like APOE4, which may make individuals more susceptible to microbial infections).

* Increased Funding and Research: The failures of amyloid-targeting trials and the growing body of evidence supporting the pathogen hypothesis have led to an increase in funding and research dedicated to this new area. Organizations like the Infectious Diseases Society of America (IDSA) have established grants specifically for research into the microbial pathogenesis of Alzheimer's.
In conclusion, the migration of researchers away from the exclusive focus on the amyloid and tau hypotheses toward the pathogen hypothesis is a major paradigm shift. It is not an abandonment of the amyloid and tau research, but rather a re-contextualization of their role within a broader, more complex picture of the disease.

This shift offers new hope for more effective treatments by targeting the potential root cause rather than just the symptoms or downstream effects.

[Ian@SI] Art, I’ve updated my data as it was a month or two old. I had misunderstood th...

Ian@SI — 8/5/2025 4:09:49 PM

Art, I’ve updated my data as it was a month or two old. I had misunderstood the 98 number of failures.
I suspect that Gemini‘s response below is only covering the data up until 2022. I’m too lazy to look at the detailed references that came with that response. :-). Ian

Based on a comprehensive review of clinical trials for Alzheimer's disease, the figure of 98 failures, specifically for Phase II and III trials targeting amyloid-beta and tau, has been cited in a significant scientific review article published in 2022. This number, which included both Phase II and III trials, reflected the state of research up to that point.
These failures, often resulting from futility analyses, underscore the immense challenge of developing effective treatments for Alzheimer's disease. A futility analysis is a statistical check during a trial to see if it's likely to succeed. If the chance of success is too low, the trial is stopped early.
The key takeaways from these numerous failures are:
* High Failure Rate: The vast majority of trials, particularly those focused on the amyloid-beta and tau hypotheses, have not yielded a successful drug.
* Futility as a Major Cause: A large number of these trials were terminated early based on futility analyses, indicating that the drugs were unlikely to show a meaningful benefit to patients.
* Re-evaluation of the Hypotheses: The consistent failures have led researchers to question the long-standing amyloid and tau hypotheses as the sole drivers of the disease, prompting a shift toward exploring other therapeutic targets and more complex disease mechanisms.
It's important to note that the exact number can fluctuate as new trials begin, fail, or succeed. However, the number 98 represents a key milestone in the history of Alzheimer's research and highlights the monumental challenges that the field has faced.

[Art Bechhoefer] It's one thing to believe tau causes Alzheimer's and another thing altogether to...

Art Bechhoefer — 8/5/2025 3:40:40 PM

It's one thing to believe tau causes Alzheimer's and another thing altogether to state that tau tangles are associated with AD. To date, there are no FDA approved drugs to clear tau, though there is at least one drug in phase 2 clinical trials that looks promising. The approved AD drugs, which treat only beta amyloid plaques, have limited success, and then only for early stage AD. I would not assume that a drug to treat tau tangles is unlikely to be successful, especially when at least one drug is already in phase 2.

Art

[Ian@SI] to believe that Tau causes Alzheimer’s disease, you have to believe that a few m...

Ian@SI — 8/5/2025 3:14:17 PM

to believe that Tau causes Alzheimer’s disease, you have to believe that a few million years of evolution has produced and retained a protein, which is deadly and causes the most undesirable death. Personally I find that very unlikely. Evolution has done a much better job with almost every other protein and probably with every other protein.

[Ian@SI] Alan, An increasing number of researchers, now believe that amyloid, beta and ta...

Ian@SI — 8/5/2025 3:06:18 PM

Alan,
An increasing number of researchers, now believe that amyloid, beta and tau are a part of the brain’s immune system. Suppressing them is more likely to allow the pathogens that do cause Alzheimer’s to more easily attack the brain then it is to produce any benefit.

Leading edge, researchers have discovered several pathogens which contribute to Alzheimer’s disease. I believe that most people here are aware of the 2008 Report in clinical trials.gov and In pubmed Has conclusively shown that people with herpes who were aggressively treated with an antiviral are up to 80% less likely to get Alzheimer’s than those who received no treatment for herpes. The virus that causes chickenpox also leads to shingles after 40 years and if you’re not aggressively treated will lead to Alzheimer’s after another 20 to 30 years. People who get Gingivitis are also prone to get Alzheimer’s. There are also some fungi and parasites which may contribute to Alzheimer’s This research is in very early stages and more evidence is needed before that can be made as an absolute statement. Research is underway to see whether getting rid of those pathogens will also act as a treatment for Alzheimer’s But the last time I checked, it was too early to get any definitive answer.

There are about 98 phase 2 and phase 3 clinical trials to get rid of amyloid, beta and or tau which have failed Outright after completion Or failed due to futility during a scheduled checkpoint. On the other hand, The Biogen Drug aduHelm, Which had two phase 3 clinical trials, one of which failed miserably and the other showed no benefit And has been withdrawn from the market as no insurance company would cover the costs And very few doctors had any interest In it and three members of the advisory committee resigned in protest.
The FDA is desperate to find something that they can approve in the Alzheimer’s area And have actually approved a couple more drugs, which tested very, very early stage Alzheimer’s. i’d be quite surprised if either of them is able to reduce the incidents of Alzheimer’s or provide any treatment for existing disease that isn’t early stage

if you use any of the AI tools, you can get excellent answers to whatever level of detail you desire. The two that I use and that I find most helpful are ChatGPT and Gemini if you use something else, I’m sure they will give you accurate information as well.

Best regards,
Ian

[A.J. Mullen] I was in too much of a hurry. Vertex has cancelled their follow-on to Journavx, ...

A.J. Mullen — 8/5/2025 12:27:10 PM

I was in too much of a hurry. Vertex has cancelled their follow-on to Journavx, which is already approved for acute pain, However, they got bad news from the FDA this morning regarding broadening the label for Journavx, fiercepharma.com “at this time, the FDA does not see a path to a broad indication,” Kewalramani (CEO of Vertex) said.

[A.J. Mullen] Vertex cancels its non-opioid pain-reliever, barrons.com. That's bad news for mo...

A.J. Mullen — 8/5/2025 9:54:45 AM

Vertex cancels its non-opioid pain-reliever, barrons.com. That's bad news for more than stockholders.

[JamesK] Both ARGX and ALNY had blow out earnings today. Doesn't seem to help the industr...

JamesK — 7/31/2025 10:29:47 AM

Both ARGX and ALNY had blow out earnings today. Doesn't seem to help the industry much though.

ATTR-CM looks like a gigantic market. ALNY BBIO PFE

[Aloner] IBRX is up more than 50% over the last 30 days and still 50% below it's 52 week ...

Aloner — 6/6/2025 9:11:15 PM

IBRX is up more than 50% over the last 30 days and still 50% below it's 52 week high. The FDA approved their drug ANKTIVA, for NMIBC, the only drug for the treatment of Bladder Cancer, with a 80% success rate, in December. They were just approved to treat Lymphopenia for Pancreatic Cancer with the same drug. They went with Trump to the Middle East and licensed their drug to the Saudi's with Trump in the room and approving the deal. Strong balance sheet, strong quarterly report. Book value is currently $2.6B. The number of new patients with NMIBC in the US alone is 61,000 per year, the fourth leading cause of Cancer in Men. Now there is a treatment.
Conduct your own due diligence, but you should do it before they get bought out.

immunitybio.com

And speaking of Bladders, UCLA just accomplished the first ever Bladder Transplant on May 4th.

[JamesK] I understand. We could both post media stories. As a biotech investor I'm waitin...

JamesK — 4/18/2025 3:37:20 PM

I understand. We could both post media stories. As a biotech investor I'm waiting more to see what direction they go with things rather than worrying about whether they have enough reviewers.

It'll take some time there to see what happens.

[DewDiligence_on_SI] At any given time, there are likely to be a few small biotech companies who have...

DewDiligence_on_SI — 4/18/2025 3:12:21 PM

At any given time, there are likely to be a few small biotech companies who have legitimate beefs with the FDA. I'm not fully convinced that this problem has become markedly worse in the past six weeks or so.

[JamesK] I have no inside information. Drug development is slowing down after FDA cuts. ...

JamesK — 4/18/2025 8:39:42 AM

I have no inside information. Drug development is slowing down after FDA cuts.

wsj.com

[DewDiligence_on_SI] investorshub.advfn.com

DewDiligence_on_SI — 4/14/2025 1:33:09 PM

[Art Bechhoefer] The FDA recently terminated 800 employees responsible for approving new drug app...

Art Bechhoefer — 4/14/2025 12:36:28 PM

The FDA recently terminated 800 employees responsible for approving new drug applications. Is it any wonder that biotech stocks, which thrive on new drug approvals, are down?

Art

[software salesperson] The Breakthrough Blood Test for Alzheimer's Disease: The p-Tau217 Biomarker for...

software salesperson — 4/14/2025 9:16:51 AM

The Breakthrough Blood Test for Alzheimer's Disease: The p-Tau217 Biomarker for Prediction and Prevention

with the recent media attention on blood tests for alzheimers, it's nice to have an explainer from Eric Topol who makes the topic semicomprehensible to this layperson. sign up with email to get the free version and comments.

it's ,the test, is available through Quest and LabCorp, among other labs.

erictopol.substack.com

[JamesK] hmmm, IGMS has about $183 million cash at last report but as far as I can tell t...

JamesK — 4/12/2025 10:33:01 PM

hmmm, IGMS has about $183 million cash at last report but as far as I can tell they don't have any products. They issue no news. I guess this is what they mean by "zombie company".

[JamesK] BIIB selling for less than 2 times sales. SRPT selling for about 2.5 times sales...

JamesK — 4/12/2025 10:21:16 PM

BIIB selling for less than 2 times sales. SRPT selling for about 2.5 times sales. REGN a bit more than 3 times sales. INCY less than 3 times sales. PFE just a little over 2 times sales. BMY just over 2 times sales. GSK just over 2 times sales.

PFE smaller market cap than AMGN.

[DewDiligence_on_SI] More on the same subject: investorshub.advfn.com

DewDiligence_on_SI — 3/21/2025 4:45:34 PM

[A.J. Mullen] Message 35074195 The FDA is still working despite the firings. It approved an ex...

A.J. Mullen — 3/21/2025 4:11:22 PM

Message 35074195
The FDA is still working despite the firings. It approved an expansion of its approval for Amvuttra yesterday to include more patients with a genetic heart condition, ATTR. It’s marketed by Alnylam who have announced aggressive pricing. At twice the rate of existing competition. Amvuttra is injected quarterly, rather than orally daily. Alynlam claims greater compliance. It silences a gene, so it gets to the root of the cause, but the difference in effectiveness seem marginal. The big difference might lie in the payment procedure within Medicare – doctors will have an incentive to prescribe the injections. finance.yahoo.com. Alnylam is up 10%.

[software salesperson] of interest to those who have or are considering uhc's medicare advantage plans:...

software salesperson — 12/30/2024 11:03:27 AM

of interest to those who have or are considering uhc's medicare advantage plans:

taken from this expose':

wsj.com

caveat emptor.

[software salesperson] Mark Cuban’s interview with Eric Topol A far-reaching discussion on how Cuban a...

software salesperson — 12/23/2024 10:52:08 AM

Mark Cuban’s interview with Eric Topol

A far-reaching discussion on how Cuban and his partner are looking to disrupt the healthcare industry thru Cost Plus. very educational.

Hopefully someone can take advantage of their knowledge on how they are either doing so or are planning to do so by eliminating pricing opaqueness, thereby saving the consumer $. Describes in detail how PBMs, insurance companies, hospitals, and transaction and administrative processors operate. Cuban was anticipating questions too quickly to be making up stuff on the fly.

costplusdrugs.com

youtube.com

en.wikipedia.org - - profile of his partner

We’ll see how successful they will be.

[software salesperson] Healthcare musings I’ll present a few articles i have been reading and then dis...

software salesperson — 12/13/2024 9:45:24 AM

Healthcare musings

I’ll present a few articles i have been reading and then discuss billing misadventures after a recent hospital stay. Then i’ll conclude with how important it is to understand the basics of medicare billing and how doing so will save you $.

Previously i presented the freakonomics podcast Message 34233866 that dealt with private equity’s takeover of 20- 30% of the healthcare system. Dubner concluded that it was a negative. So let’s start there.

Here is a conservative rebuttal:

cremieux.xyz

Here is a nyt article by Helen Ouyang claiming that healthcare billing systems are destroying doctor/ patient trust. I don’t think the conclusion follows from the premise.

What Doctors Like Me Know About Americans’ Health Care Anger

I rushed around the patient as he lay motionless with his eyes closed in the emergency room. He was pale and sweaty, his T-shirt stained with vomit. You didn’t have to be a health-care worker to know that he was in a dire state. The beeps on the monitor told me his heart rate was dangerously slow. I told the man that he was going to be admitted to the hospital overnight.

After a pause, he beckoned me closer. His forehead furrowed with concern. I thought he would ask if he was going to be OK or if he needed surgery — questions I’m comfortable fielding. But instead he asked, “Will my insurance cover my stay?”

This is a question I can’t answer with certainty. Patients often believe that since I’m part of the health-care system, I would know. But I don’t, not as a doctor — and not even when I’m a patient myself. In the United States, health insurance is so extraordinarily complicated, with different insurers offering different plans, covering certain things and denying others (sometimes in spite of what they say initially they cover). I could never guarantee anything.

I didn’t say all this to the man, though, because I needed him to stay in the hospital and accept inpatient treatment. So instead I hedged. “You’re very sick,” I told him. “You shouldn’t worry about your insurance right now.” I should have been able to give him a better answer, under a better system.

The killing of Brian Thompson, the chief executive of UnitedHealthcare, the country’s largest health insurer, has reignited people’s contempt for their health plans. It’s unknown if Mr. Thompson’s tragic death was related to health care, and the gleeful responses have been horrifying. But that reaction, even in its objectionable vitriol, matters for how it lays bare Americans’ deep-seated anger toward health care. Around the country, anecdotes were unleashed with furor.

Among these grievances is the great unknown of whether a treatment recommended by a doctor will be covered. It’s critical for me as a physician to build trust with my patients by giving them clear answers. But the conversations we’re seeing now about health care remind me that insurance unknowns don’t just compromise the care I can deliver to my patients — they also undermine the fragile doctor-patient trust. It’s an unsustainable dynamic.

Unsurprisingly, despite my platitudes, my patient did worry. Instead of resting on the stretcher, he and his wife began calling his insurance company. To keep him from leaving, I tried to be more persuasive, even though I didn’t know what kind of health plan he had: “I’m sure your insurance will pay. I’ll document carefully how medically necessary this admission is.” I added that social workers and other advocates could also assist in sorting out his insurance once he was admitted. And worst-case scenario, if they couldn’t, I crossed my fingers that the hospital’s charity care would help.

I said what I could to get him to stay, but I understood why he wanted to be certain. The average cost of a three-day hospital stay is $30,000. He had heard the health insurance horror stories. Maybe he had lived through one himself.

One of my first lessons as a new attending physician in a hospital serving a working-class community was in insurance. I saw my colleagues prescribing suboptimal drugs and thought they weren’t practicing evidence-based medicine. In reality, they were doing something better: practicing patient-based medicine. When people said they couldn’t afford a medication that their insurance didn’t cover, they would prescribe an alternative, even if it wasn’t the best available option.

As a young doctor, I struggled with this. Studies show this drug is the most effective treatment, I would say. Of course the insurer will cover it. My more seasoned colleague gently chided me that if I practiced this way, my patients wouldn’t fill their prescriptions at all. And he was right.

I’ve been on the other side of the American health insurance quagmire, too, as a patient. Recently, my primary care physician recommended I undergo additional testing to assess my risk for certain diseases. The patient in me instinctively asked if my insurance covered it, even though I knew she wouldn’t know the answer. “They should,” she said. “It seems most insurers are paying for it.” I recognized her response — it’s the same optimistic but vague one I often give.

When doctors can’t give a straight or accurate answer, patients may lose faith in them. What’s more, when insurers reject claims, they usually blame the provider — the medical code used was wrong, the diagnosis wasn’t specific enough — which can further erode the relationship between patients and their doctors.

I saw this happen with my mother. She got her annual flu shot, which is part of her preventive care — a proactive step we want patients to take — but her insurance said it wasn’t covered because her doctor supposedly used the wrong code. The clinic resubmitted the claim, but it continued to be denied. Each time my mother called her insurance company, an agent blamed her doctor. Eventually, my mother grudgingly returned to her physician for her annual exam, but her relationship with the primary care practice has frayed. She no longer gets her vaccines there.

My one family member with solid insurance is my dog. He got elective surgery recently, and I was astounded by the straightforward nature of his insurance. Once we meet the deductible, everything is simply covered by 80 percent. This is clearly described in a packet I received when I first signed him up. It’s an imperfect comparison to insurance for humans — I pay in full first, then get reimbursed — but it’s incredible to think that insurance for pets and possessions is easier to navigate and more consumer-friendly than insurance for people.

The country is not heading toward a single-payer system, but that doesn’t mean we have to continue leaving patients and their doctors in the dark. I loathe the fact that patients can’t automatically get the care they need without thinking about costs. But they at least deserve clarity about what’s covered before they acquiesce to expensive tests and treatments. Health insurance shouldn’t be so opaque, up to the whims of different companies. Coverage shouldn’t be so convoluted, mired in rigid codes and obfuscating wording. I should be able to tell my patient in the E.R. if his hospital stay will definitely be paid for. I know exactly how much of my dog’s care will be covered; why can’t I know the same for my patients?

In the end, my patient in the E.R. decided to go home that day. I reiterated how sick he was. I showed him the results that concerned me, and even tried to tell him that he could possibly die if he left the hospital. But I’m not sure how much he trusted me after my overconfident assurances that his insurance would pay; when he finally got through to an agent, he was told coverage would depend on the specifics of his care.

He couldn’t risk a big hospital bill right now, he told me, matter-of-factly. He promised to come back if he felt worse.

—---------------

What she fails to mention is the fact that some providers are unreachable by phone and if you can, they generally know little or nothing about how bills are calculated. If bills are incorrect, i write them a short note explaining why i’m not paying them until they are corrected. Billing patients is the easiest course of action. Some people actually pay them because they don’t understand them.

A recent 4 day hospitalization of mine had ~ $ 40,000 contractual medicare writeoff and a few hundred dollar sequestration writeoff. No wonder there is antagonism and people have “encounters” with the system.

So if you don’t understand the basics of medicare billing, i suggest you learn one day at a time and question all invoices. This point applies to everyone involved in the process - - hospitals, doctors, ambulances, etc. Since billing is the easiest course and no one in the system talks to anyone else, often the problem is they don’t even have your correct address or medicare number.

In my case, i exceeded my annual medicare part A deductible of 1632 and part B deductible of 240.

Oh, they wanted to have an “encounter”. Ok. so I sent them this letter:

—-- hospital final reconciliation

You recently sent me a revised letter because medicare made an error and didn’t charge me a cash deductible of 1632 for claim #----------. You then rebilled them. This is the correct amount so i will pay it. Medicare had initially said their claim was bogus and that i owed 0.

Any associated —----hospital doctor practices have been paid out of ~ $45,000 or my secondary insurance, —---- So they will not be paid again by me.

You have also billed me ~ 54 for claim # —----This is incorrect.

You should be billing my secondary insurance, —------. Thus, i will not be paying you ~ 54.

This concludes our recent business.

—------------------------------------------------------

Update - - re: your late incorrect charges for drs. —------, you should also be billing my secondary insurance, —----, not me. Thus, i will not be paying you for these incorrect invoices.

This concludes our recent business.

—--------------------

Since there is a lag in the hospital’s receipt of payments from secondary insurance, i continued to receive bills, collection notices and other “threatening” letters. eventually they must have gotten paid since the letters stopped.

Moreover, my secondary insurance pays for all medical invoices unrelated to this hospital stay through 2024 since i exceeded my annual deductible. So i’ve sent similar letters to those providers as well and toss their invoices.

As you can see, the system is rife with errors by medicare, and the hospital. Also ambulances, more doctors, etc.

So buyer beware and good health to all.

[Sun Tzu] Good morning. Several of my biotechs are leaping tall buildings in a single boun...

Sun Tzu — 12/2/2024 10:07:21 AM

Good morning.
Several of my biotechs are leaping tall buildings in a single bound
This is just FYI - Message 34932909

[JamesK] RFK making dividends great again. PFE 6.77% GSK 4.62% BMY 4.27% Others like AMG...

JamesK — 11/16/2024 5:13:15 PM

RFK making dividends great again. PFE 6.77% GSK 4.62% BMY 4.27%

Others like AMGN GILD JNJ in the 3's. ROCHE 3.75%

[Art Bechhoefer] If there is a pattern in what often becomes a major fall in market value of a st...

Art Bechhoefer — 11/10/2024 11:41:45 AM

If there is a pattern in what often becomes a major fall in market value of a stock, the causes of that pattern should be taken together, not singling out one or more.

For example, NTLA, which you mentioned, was also on my list of potentially what's hot and what's not. Long before announcing they were in phase 1 testing of an oral drug that would work like the injected drugs for reducing obesity, regulating diabetes II, and performing other "miracles" that could benefit the heart, kidneys, and liver as well, NTLA had begun clinical trials on CRISPR type gene editing in vivo, with the promise of being much less costly than the currently popular ex vivo methods. But NTLA, also like many other small development stage biotech stocks, had a cash flow problem. When cash burn is so high that the only way to fix it is to issue more shares, diluting potential earnings, that's when a previously overvalued stock drops like a ton of bricks.

That's what happened to NTLA, down drastically from earlier values. So an investor has to consider at least two factors: Does the company have something glamorous, like a cancer or obesity treatment? Does the company have enough money to bring its potential drug to market, at a cost running upwards from $500 million? If not, you know where it's most likely to head.

Art

[JamesK] Wasn't meant to be comprehensive. I didn't screen names. Was off the top of my h...

JamesK — 11/9/2024 6:37:28 PM

Wasn't meant to be comprehensive. I didn't screen names. Was off the top of my head.

It's interesting to look at some names that seem insane. NTLA was 200 back then.

[Aloner] CRVS should be on your list.

Aloner — 11/9/2024 12:21:45 AM

[JamesK] ALNY ARGX RVMD AMGN VRTX REGN VKTX Just posting a few names that have exceeded t...

JamesK — 11/8/2024 7:34:41 PM

ALNY ARGX RVMD AMGN VRTX REGN VKTX Just posting a few names that have exceeded their 2021 highs. Just looking at bigger caps. GILD did too but I don't count it since it was higher before that. SRPT has not. MDGL should be listed but didn't really have a 2021 peak like most of them.

KYMR has rallied a lot but is well short of it's 2021 high.

[software salesperson] nature.com the effects of GLP-1 agonists across the economy. one nugget: And...

software salesperson — 11/5/2024 11:49:40 AM

nature.com

the effects of GLP-1 agonists across the economy.

one nugget:

And some lawmakers, including in the United States, are beginning to push back on the high costs, particularly after an analysis found that Novo Nordisk could sell Ozempic for $5 per month and still make a profit.

[Aloner] KZIA is up 348% on the week. A small Biotech that announced positive Phase II cl...

Aloner — 7/13/2024 9:33:46 PM

KZIA is up 348% on the week. A small Biotech that announced positive Phase II clinical trial results for the treatment of GBM and DIPG. The largest volume leader for the day on Wednesday, with 440 Million shares traded. More than NVDA, MSFT and APPL . Combined. Traded as high as $1.58 on Thursday and closed for the week at $0.90 after some profit taking on Friday. It started the week at $0.20/Share, and has an all time high of $11.48 from 5 years ago. Listed on NASDAQ, it received a 180 day extension for trading under $1.00, good until October.

[A.J. Mullen] Good results from a Phase 3 trial of Vutrisaran, an RNAi therapy against ATTR ca...

A.J. Mullen — 6/24/2024 1:15:26 PM

Good results from a Phase 3 trial of Vutrisaran, an RNAi therapy against ATTR cardiomyopathy, give 35% boost to shares of Alnylam. It reduced deaths and recurrent CV events compared to both a placebo and standard of care (tafamidis).
https://www.wsj.com/livecoverage/stock-market-today-dow-sp500-nasdaq-live-06-24-2024/card/alnylam-soars-on-positive-heart-drug-data-G48zzAL966gHgeS0F0VA?siteid=yhoof2
https://finance.yahoo.com/news/alnylam-claims-success-closely-watched-082000187.html

[software salesperson] Study Suggests Genetics as a Cause, Not Just a Risk, for Some Alzheimer’s People...

software salesperson — 5/7/2024 10:45:27 AM

Study Suggests Genetics as a Cause, Not Just a Risk, for Some Alzheimer’s
People with two copies of the gene variant APOE4 are almost certain to get Alzheimer’s, say researchers, who proposed a framework under which such patients could be diagnosed years before symptoms.

A C.T. scan of a patient with Alzheimer’s disease.Credit...Vsevolod Zviryk/Science Source

By Pam Belluck

May 6, 2024

Scientists are proposing a new way of understanding the genetics of Alzheimer’s that would mean that up to a fifth of patients would be considered to have a genetically caused form of the disease.

Currently, the vast majority of Alzheimer’s cases do not have a clearly identified cause. The new designation, proposed in a study published Monday, could broaden the scope of efforts to develop treatments, including gene therapy, and affect the design of clinical trials.

It could also mean that hundreds of thousands of people in the United States alone could, if they chose, receive a diagnosis of Alzheimer’s before developing any symptoms of cognitive decline, although there currently are no treatments for people at that stage.

The new classification would make this type of Alzheimer’s one of the most common genetic disorders in the world, medical experts said.

“This reconceptualization that we’re proposing affects not a small minority of people,” said Dr. Juan Fortea, an author of the study and the director of the Sant Pau Memory Unit in Barcelona, Spain. “Sometimes we say that we don’t know the cause of Alzheimer’s disease,” but, he said, this would mean that about 15 to 20 percent of cases “can be tracked back to a cause, and the cause is in the genes.”

The idea involves a gene variant called APOE4. Scientists have long known that inheriting one copy of the variant increases the risk of developing Alzheimer’s, and that people with two copies, inherited from each parent, have vastly increased risk.

The new study, published in the journal Nature Medicine, analyzed data from over 500 people with two copies of APOE4, a significantly larger pool than in previous studies. The researchers found that almost all of those patients developed the biological pathology of Alzheimer’s, and the authors say that two copies of APOE4 should now be considered a cause of Alzheimer’s — not simply a risk factor.

The patients also developed Alzheimer’s pathology relatively young, the study found. By age 55, over 95 percent had biological markers associated with the disease. By 65, almost all had abnormal levels of a protein called amyloid that forms plaques in the brain, a hallmark of Alzheimer’s. And many started developing symptoms of cognitive decline at age 65, younger than most people without the APOE4 variant.

“The critical thing is that these individuals are often symptomatic 10 years earlier than other forms of Alzheimer’s disease,” said Dr. Reisa Sperling, a neurologist at Mass General Brigham in Boston and an author of the study.

She added, “By the time they are picked up and clinically diagnosed, because they’re often younger, they have more pathology.”

People with two copies, known as APOE4 homozygotes, make up 2 to 3 percent of the general population, but are an estimated 15 to 20 percent of people with Alzheimer’s dementia, experts said. People with one copy make up about 15 to 25 percent of the general population, and about 50 percent of Alzheimer’s dementia patients.

The most common variant is called APOE3, which seems to have a neutral effect on Alzheimer’s risk. About 75 percent of the general population has one copy of APOE3, and more than half of the general population has two copies.

Alzheimer’s experts not involved in the study said classifying the two-copy condition as genetically determined Alzheimer’s could have significant implications, including encouraging drug development beyond the field’s recent major focus on treatments that target and reduce amyloid.

Dr. Samuel Gandy, an Alzheimer’s researcher at Mount Sinai in New York, who was not involved in the study, said that patients with two copies of APOE4 faced much higher safety risks from anti-amyloid drugs.

When the Food and Drug Administration approved the anti-amyloid drug Leqembi last year, it required a black-box warning on the label saying that the medication can cause “serious and life-threatening events” such as swelling and bleeding in the brain, especially for people with two copies of APOE4. Some treatment centers decided not to offer Leqembi, an intravenous infusion, to such patients.

Dr. Gandy and other experts said that classifying these patients as having a distinct genetic form of Alzheimer’s would galvanize interest in developing drugs that are safe and effective for them and add urgency to current efforts to prevent cognitive decline in people who do not yet have symptoms.

“Rather than say we have nothing for you, let’s look for a trial,” Dr. Gandy said, adding that such patients should be included in trials at younger ages, given how early their pathology starts.

Besides trying to develop drugs, some researchers are exploring gene editing to transform APOE4 into a variant called APOE2, which appears to protect against Alzheimer’s. Another gene-therapy approach being studied involves injecting APOE2 into patients’ brains.

The new study had some limitations, including a lack of diversity that might make the findings less generalizable. Most patients in the study had European ancestry. While two copies of APOE4 also greatly increase Alzheimer’s risk in other ethnicities, the risk levels differ, said Dr. Michael Greicius, a neurologist at Stanford University School of Medicine who was not involved in the research.

“One important argument against their interpretation is that the risk of Alzheimer’s disease in APOE4 homozygotes varies substantially across different genetic ancestries,” said Dr. Greicius, who cowrote a study that found that white people with two copies of APOE4 had 13 times the risk of white people with two copies of APOE3, while Black people with two copies of APOE4 had 6.5 times the risk of Black people with two copies of APOE3.

“This has critical implications when counseling patients about their ancestry-informed genetic risk for Alzheimer’s disease,” he said, “and it also speaks to some yet-to-be-discovered genetics and biology that presumably drive this massive difference in risk.”

Under the current genetic understanding of Alzheimer’s, less than 2 percent of cases are considered genetically caused. Some of those patients inherited a mutation in one of three genes and can develop symptoms as early as their 30s or 40s. Others are people with Down syndrome, who have three copies of a chromosome containing a protein that often leads to what is called Down syndrome-associated Alzheimer’s disease.

Dr. Sperling said the genetic alterations in those cases are believed to fuel buildup of amyloid, while APOE4 is believed to interfere with clearing amyloid buildup.

Under the researchers’ proposal, having one copy of APOE4 would continue to be considered a risk factor, not enough to cause Alzheimer’s, Dr. Fortea said. It is unusual for diseases to follow that genetic pattern, called “semidominance,” with two copies of a variant causing the disease, but one copy only increasing risk, experts said.

The new recommendation will prompt questions about whether people should get tested to determine if they have the APOE4 variant.

Dr. Greicius said that until there were treatments for people with two copies of APOE4 or trials of therapies to prevent them from developing dementia, “My recommendation is if you don’t have symptoms, you should definitely not figure out your APOE status.”

He added, “It will only cause grief at this point.”

Finding ways to help these patients cannot come soon enough, Dr. Sperling said, adding, “These individuals are desperate, they’ve seen it in both of their parents often and really need therapies.”

[software salesperson] erictopol.substack.com A Big Week for GLP-1 Drugs A Breakthrough Award, Ne...

software salesperson — 5/3/2024 9:51:30 AM

erictopol.substack.com

A Big Week for GLP-1 Drugs A Breakthrough Award, New Evidence in Parkinson's and Heart Disease

ERIC TOPOL

APR 06, 2024

coming a bit late on this one.

[JamesK] Sorry don't follow them but they have a $5 billion plus market cap so they must ...

JamesK — 5/1/2024 5:19:09 PM

Sorry don't follow them but they have a $5 billion plus market cap so they must be doing something right.

[Aloner] IBRX anyone? Any holders, buyers, sellers, opinions, suggestions, complaints or ...

Aloner — 4/26/2024 8:04:27 PM

IBRX anyone? Any holders, buyers, sellers, opinions, suggestions, complaints or analysis? Seems like some really good news lately and the market reflects it. Thinking about dipping my toes in after a dip. Any intelligent discourse is greatly appreciated.

[JamesK] Yes. Compare VINC to the great VKTX offering. The xbi run up over 100 has allow...

JamesK — 4/26/2024 10:34:02 AM

Yes. Compare VINC to the great VKTX offering. The xbi run up over 100 has allowed quite a bit of them to refinance. Most of the better ones at least did some kind of decent offering to keep them going if things stay tough for awhile.

[Sun Tzu] That's how it always goes with biotechs. If they can't license the drug, they ha...

Sun Tzu — 4/25/2024 8:03:32 PM

That's how it always goes with biotechs. If they can't license the drug, they have to issue shares to survive because there is no other source of funds. So the bad news never ends with the trial not being any good.

[JamesK] VINC - sorry I ever mentioned this one. After declining all the way back down th...

JamesK — 4/25/2024 4:39:55 PM

VINC - sorry I ever mentioned this one. After declining all the way back down they want to do an offering.

[Sun Tzu] Wow! Amazing!

Sun Tzu — 3/29/2024 12:00:47 AM

[JamesK] VINC was .61 at bottom in the bio bear. Now over 9. There's a lot of these littl...

JamesK — 3/11/2024 11:39:55 AM

VINC was .61 at bottom in the bio bear. Now over 9. There's a lot of these little ones that have had really big moves. Even VKTX was in the 2's just a few months ago.

[JamesK] VKTX - up on take over rumor. Seems unlikely before we see data on their drugs. ...

JamesK — 2/16/2024 4:57:10 PM

VKTX - up on take over rumor. Seems unlikely before we see data on their drugs. Years ago GILD bought Pharmasset for $11 billion. That was a multi billion dollar drug for GILD.

If (a big if) VKTX drug were better than Lilly drug then what is this company worth? If better than Lilly drug isn't it almost certain to be a $10 billion a year drug?

So, what is VKTX worth in a buyout?

Phase III should go really quick for enrollment.

[Aloner] ARGUS Opinion: Since 2021, the biotechnology industry has underperformed the bro...

Aloner — 1/24/2024 12:50:18 PM

ARGUS Opinion:
Since 2021, the biotechnology industry has underperformed the broader market, reversing a multi-year trend that had seen superior returns since coming out of the Great Recession. In 2021 and 2022, the equal-weight SPDR Biotech ETF (XBI), which includes more small-cap, development-stage companies, declined 21% and 26%, respectively, compared with a 27% gain and 18% decline for the S&P 500, including dividends. The trend continued in 2023, with XBI gaining 8% compared with a 24% advance for the S&P 500. We attribute the underperformance, particularly for development-stage companies, to factors including a "risk-off" environment amid elevated inflation and increasing interest rates, which contributed to challenging financing markets and a near closing of the IPO window. As well, an elevated number of biotech companies traded below their cash reserves and explored strategic alternatives or bankruptcy. We note increased scrutiny over runaway drug pricing weighing on the industry. But the tide may be turning. Biotech has been on fire since bottoming a few months ago, with the iShares Nasdaq Biotech (IBB) surging 20%-plus and printing a minor breakout of its range back to January 2022. Looking ahead, mergers and acquisitions (M&A) and the ability to raise capital are major keys to growth in the industry. We are encouraged by the return of some larger scale M&A deals and a seemingly healthy appetite for deals from larger biotech and big pharma players, as a new wave of patent expirations for many high-revenue-generating medicines is expected in the second half of the decade.

[software salesperson] additional reasons over and above fewer side effects that novavax is better than...

software salesperson — 1/21/2024 9:45:48 AM

additional reasons over and above fewer side effects that novavax is better than MRNA covid vaccines.

via michael lin, stanford.

1 ) 3x RNA vaccines induce IgG4 antibodies, which clear antigens poorly and is associated with immunotolerance. By contrast, 3x Novavax does not induce IgG4.

2) And here's a recent review on Novavax having fewer side effects "Evidence suggests that NVX-CoV2373, when utilized as a heterologous booster, demonstrates less reactogenicity compared with mRNA vaccines."

3) Here's the evidence the Novavax vaccine format may induce broader responses (more protective to future variants). Note was studied with the first Novavax vaccine (Wuhan D614G) against Omicron as the variant.

4) But RNA has cytotoxic T cell responses. So I had said that personally I will try getting them in alternate years to get the best of both.

5) Today's results provide another reason potentially to alternate. It also suggests Novavax would be better if we ever need 2 vaccines within a year. Given how fast variants are evolving, FDA should consider providing people that option.