r/Biotechplays

Alpha Tau Medical [nasdaq: DRTS] is going to host a conference call Monday AM regarding the preliminary results from their recurrent GBM (inoperable brain cancer) trial.

The shareholders didn't expect this but are taking it as potentially very good news because the remaining cases (they've moved from Ohio to NYC) are still scheduled. The question is, "How good is the news?" We'll have to attend the call to find out so I put together a cheat sheet for those that are wondering what to listen for when considering rGBM progress.

As you're aware, this is not a drug company. This is a medical device company. They use physics (alpha radiation delivered in nanometer level targeting directly into solid tumors) rather than chemistry. If their hyper-local physics don't destroy nearby tissue or the immunity system, then any positive results they get mean that the DaRTs can be used in conjunction with other therapies. That's a very good thing.

More on the rGBM below but for those that haven't heard of Alpha Tau (DRTS), here's a quick primer...

They have already received PMDA (Japan's FDA) certification for Head & Neck cancers, so it's a real platform that provides oncologists with a new tool.

They have been on an insane hot streak since receiving PMDA.

Alpha Tau got approval from the FDA for testing with Keytruda, Merck's $30B baby, and quickly demonstrated a massive (2x, 3x) efficacy increase.

They compiled the results from their Pancreatic Cancer trials which showed an extremely impressive 100% DCR (disease control response.) It is believed they have completed nearly 100 cases of late, late stage PanC and have now been approved for new trials in Japan, France, Italy and Canada.

The FDA has granted five modules for Alpha Tau which includes trials for brain, pancreas, prostate and other solid cancers, either alone or in conjunction with other therapies.

Over the past year, they've run up a gaudy 200%+ and still maintain a market cap of only $750M.

And, because it's rGBM, there is a possibility that the recurring GBM cancer initial trial data changes everything.

THERE ARE NO GOOD TREATMENTS FOR rGBM.

When a neuro-oncologist faces a recurrent GBM case, they are not choosing between good and better options — there is no standard of care, and all available treatments are considered non-curative. They are managing a patient who has already survived longer than most, whose tumor has now outsmarted surgery, radiation, and chemotherapy, and who is almost certainly going to die from this disease. After first-line therapy fails, median progression-free survival is 1.5 to 6 months and median overall survival is 2 to 9 months. The oncologist's toolkit at this point — more chemotherapy, re-irradiation, or bevacizumab — may slow things briefly but changes nothing fundamental. Recurrent GBM is widely considered one of the most disappointing fields in oncology, where decades of research have yielded no meaningful survival benefit. The honest conversation an oncologist has with an rGBM patient is not about getting better. It is about how much time remains, and how to spend it.

Back to Alpha Tau and the hope for hope where none exists...

There have been 3 cases in the 10 person trial so far; all out of Ohio. The remaining 7 will be done in New York City starting this month. We aren't looking for survivability duration. What we're looking for is:

Safety: The procedure (outpatient typically) can be done without causing harm to the brain or immunity system. You'll know it's solid if the patient walks out on their own power within 48 hours of the procedure and follow up testing.

Coverage: How much of the tumor was hit with the targeted radiation? We're looking for 80%+ coverage of the tumor. Hit the tumor hard with high-LET Alpha Radiation.

And we're expecting that the MRI's taken of these initial patients have shown something worth sharing with shareholders but you'll need to understand how to evaluate initial results.

Initial results = RANO

When you're dealing with rGBM, there is a standardized way of understanding trial results called RANO 2.0. RANO is Response Assessment of Neuro-Oncology and it is a standard globally that looks at an MRI taken after treatment to determine whether the tumor has grown, shrunk, how much and whether continued treatment with corticosteroids is needed, etc.

RANO terms to listen for on the conference call:

Stable Disease (SD) No new lesions. No increase in corticosteroid use. Clinical status is seen as stable. If the tumor shrinks but by less than 50%, or stays roughly the same size, you have stable disease. In a cancer as aggressive as rGBM, halting progression is clinically meaningful — but of the four outcomes discussed here, SD is the most modest signal for investors.

Partial Response (PR) The tumor has shrunk by at least 50%. This is incredibly rare and would be considered fantastic news. Even one of the three patients achieving a PR would be a reset for DRTS because it means that there is (FINALLY) a potential way of seriously shrinking the GBM tumor.

Complete Response (CR) A complete obliteration of the tumor. Such a result would be a landmark in rGBM oncology. Nobody should expect this but everyone should understand that this is the dream. The whole world of oncology changes overnight if there is a CR on any one of the three patients.

Abscopal Effect This is a mythological creature. Remember that Alpha Tau's DaRT therapy is a local treatment, meaning that they're inserting the radium-covered darts directly inside a single tumor. There have been, over the past few years, a few odd cases where oncologists noticed the strange reality that distant, untreated tumors responded to the local DaRT treatment. The current thinking is that local tumor destruction releases tumor antigens that prime the immune system to recognize and attack the same cancer elsewhere in the body. Again, nobody expects to see abscopal effects on the first three patients but if you hear it on the call, you know what they're talking about.

So, you have a stock that is up 200% over the past year, it's not a typical biotech stock because it's a device, it has achieved cert in Japan, it has shown phenomenal initial results with Pancreatic cancer and it's on the verge of announcing something positive in recurring GBM. The market cap is $750M and typical M&A in the radiotherapy space goes for $4B.

Hit me up with any questions. Not a medical professional. Not financial advice. And yes, I'm irresponsibly long on this stock because fck cancer.

Hi everyone! New account - I have been recently getting more involved in the biotech/pharma investing space and was curious as to what people think. I've been trying to use my background as a clinical pharmacist to supplement my financial analyses, and wanted to see how my analyses pan out and learn from it.

I've been following ATYR stock for quite some time now shortly after its prices plummeted late last year after the results of their Phase 3 trial. I had personally invested just a little bit when it hit $1 and recently when it was hovering around $0.80. My original thought process was that the company wasn't completely dead yet and had a decent chance for a rebound based on these factors:

• Novel drug to treat pulmonary sarcoidosis, where the first line treatment is steroids (comes with nasty side effects with long term use)
• Good secondary outcomes, although it failed to meet its primary endpoint in a mean reduction of corticosteroid use, it did improve FVC and KSQ Lung Scores. I think what we typically see in diseases that are harder to treat (like oncology/rheumatology), the FDA is more flexible with what metrics make a drug clinically viable (symptom improvement/quality of life). It surely was different from what they intended, in reducing steroid doses, but it sounded like it would still have a role in therapy as an adjunct agent?
• Ambiguity regarding it's lead asset sounds like a terrible thing, but it wasn't shut down for good, and the stock price was kinda tempting to me post crash (Sorry if you had invested). It looked like ATYR had a pretty high liquidity and somewhat decent sized runway to continue operating its other ongoing trials.

After combing through some posts related to ATYR it seemed like it was split on two extremes, your overenthusiastic, annoying, "to-the-moon" type posts and your "i would rather have a gun to my head rather than invest in ATYR again." To be honest, the latter made more sense to me as there were so many people who got burned, but my take was somewhere more in the middle, and it has stayed pretty constant since I made my initial investments months ago.

The outcome of the FDA type C meeting was more or less what I thought would happen (a complete redo of the phase 3 trial reframing their primary endpoints). People who were talking highly of this stock claimed that it's secondary endpoints would carry it to the finish line and get it approved despite failing primary endpoints, with some nonsense about "new" FDA standards, but realistically there are so few drugs that have ever had success with this. Secondary endpoints are generally considered exploratory and I felt like while they had merit and highlighted a potential role in therapy for Efzofitimod, that it would still require a redo of the Phase 3 trial to reframe their primary endpoints. The realistic best case scenario would have been maybe a narrower study group, but the fact that a redo is happening at all still gives it a chance.

My biggest concern for my continued investment is their funding. Their annual expenses rounded out to close to $60 million, and it seemed like they'd only have maybe a year, a little more over a year of runway left, so a complete re-do, and the time it takes to enroll patients and carry it out would likely exceed their funding. Although typical for biotech companies to have massive R&D spend with little revenue, the public sentiment, the pending lawsuits (add that to the expenses), and the risk of delisting from NASDAQ (potential reverse stock split and dilution incoming?) does make me skeptical. I noticed they had a milestone partnership with Kyorin, a mid-sized Japanese pharmaceutical company, but to what degree in the event of a redo of their Phase 3 trial?

Would love to have discussions about this from both ends of the spectrum. Please let me know if there are other factors i'm missing. In the best case scenario, they find the capability to fund a new phase 3 trial, would you invest? Sorry for the super long post!

Word is Marty Makary is getting the ax. Politico's Rachel Bade dropped the scoop May 6, two well-placed sources expressed confidence Makary is on borrowed time. Bloomberg ran the "paranoia, turmoil and backlash" deep dive a day earlier.

The political driver is flavored vapes. Trump wants them approved, Makary blocked the agenda, White House insiders now call him a thorn.

The biotech driver is messier. Sanofi just yanked Tzield from the Commissioner's National Priority Review program after a high-level disagreement. That is a public humiliation of Makary's flagship program. Replimune's RP1 melanoma rejection lit up the industry over single-arm trial pushback.

Vinay Prasad already exited CBER end of April. Atara's Ebvallo got a positive Type A meeting one week later, FDA agreed a single-arm study with appropriate historical control could support approval. The reversals are already starting.

What it means for the M&A Hunter universe

Randomized trial designs get a relative bid. Single-arm submissions face structural headwinds. Companies that built proper Phase 3 randomized programs are insulated. The OnPrime/GOG-3076 type structure becomes the gold standard.

Cell therapy and gene therapy get a tailwind. The Atara reversal is the template. Post-Prasad, the agency is already walking back some of the most aggressive denials. If Makary follows him out, more reversals likely.

Q3-Q4 PDUFA dates carry transition risk. Leadership change in the middle of a review window can cut either way. Industry-friendlier commissioner, neutral to positive. More restrictive RFK Jr. pick, short-term overhang. PDUFA dates in August through November are the ones to watch.

The bigger pattern

Makary came in promising speed. Industry got blindsided by setbacks. Internal staff describe culture clashes. The agency that approves your drug needs to be predictable. Right now it is anything but.

Watching this closely.

DO NOT CHASE THE NEWS Trim crazy pops