PD

MediumSinger8088

This is a pretty good board. Though I respectfully disagree with some posters about the probability of Gain going it alone vs. a partnership vs. selling the company in 2026, the quality of the discussion and consideration of data along with alternative reads on the future, is good - and there are more contributors lately, which is a welcome change. What I'm looking for in terms of data in 2026: I'd love to see MDS-UPDRS part 3 median changes (NOT MEAN, median, which is much more relevant for small numbers in a skewed distribution) from baseline in the continuation study reach an MCID (minimal clinically important difference) of 3.25 relative to historical norms for early PD trials where the drug is started in the "levadopa on" state. Many trials consider -3 as "minimal improvement" and +4 as "minimal worsening" (remember part 3 is a 132 point scale with 18 motor functions assessed by a trained physician, not patient self-reported). Right now the median change from baseline is = -2.56 with an expectation value of +0.6 based on historical norms in a hypothetical placebo group (assumptions: Part 3 change +0.6 every 3 months; +2.4 points / year). Thus we're already at about 3.20 for the delta. So all the MDS-UPDRS need do is stay stable relative to baseline and the delta will increase. THIS IS NOT THE SAME AS HAVING A REAL PLACEBO GROUP and FDA usually discounts historical control comparisons - but meeting such threshold would massively increase my personal confidence that the drug is working. If the estimated difference from historical norms hits 4 or 5, it's a whole new day. Any additional biomarker data present at conferences and so forth would be gravy.

IntradayGuy

Watch the video's he gets pushed/bumped out of the way by her driving and not obeying commands... Im not advocating for her being killed but go do this to your local PD any day of the week you can get dead too by them

MediumSinger8088

AI assist to question of cost for a Phase 2 trial: $15-45 million. A "lean" trial might be $6-15 million. There's a BMJ analysis (2020 Jun 11;10(6):e038863. doi: [10.1136/bmjopen-2020-038863](https://doi.org/10.1136/bmjopen-2020-038863)). Much smaller cost than paying market cap + premium. Big pharma would say "cool early work, find the money to prove it out in phase 2 then, if you can, come see us". Or agree to support some cost and provide resources in exchange for exclusive license to market for PD. Something like that. Cheaper than forking out hundreds of millions. Why buy the cow when you can get the milk ... if not for free, for much less cash.

microcapreturns

Since they are at least 180 days in with some patients and they are presenting this data in March at AD/PD I would guess they are happy with it. I expect data to continue to improve and if the nonresponders don't continue in trial the 180 data suddenly gets much better.

microcapreturns

Extension data at AD/PD in March. I also told the company they should have included those 3 and just note no final lumbar tap. It's not pleasant from what I have been told. I also asked about the 3 outliers in the data and they seemed like they knew exactly what was happening. Did you run the data without them in it?

Cautious_Room1910

Forgive me, can you tell me where you read in the publication that only 1 of the participants with a reduction in GluSph is a GBA1 case, 4 are idiopathic, and 2 are other cases? I can’t find this information. First of all, I would like to talk about BIAL: if I’m not mistaken, it is precisely in the PubMed article linked by the other person in the conversation that they show a 2x increase in GCase activity in patients with GBA1 Parkinson’s after 28 days, whereas, although different in the way and consequences, in the case of another drug and phase 1a, GCase activity increased by about 50% with GT. So in sick patients, the BIAL molecule reaches the right tissues and correctly activates GCase (I cannot speculate on whether this results in more or less effect than GT, despite the excellent numbers). This is an extremely promising data point regarding what the drug is precisely trying to achieve (i.e., not preclinical studies in animals that do not have a chronic disease course like in humans and cannot or should not influence proper financial decisions!). Regarding the concern raised by the other user about the transient increase in GluCer with BIAL’s drug, I would not worry, because, as also stated directly in the PDF published by Gain on January 6: page 20, "Reducing GluCer levels has no clinical effect in GBA-PD." In any case, just a few more months to see who will be right regarding the release of the data, noting that, being a private company in an already delicate sector, they are not absolutely required to release biomarker information to the public, and so far this has been the case. Furthermore, their phase 1 study was very short, so if this did not allow presenting useful data, we should at least keep the door open. Now, if it is true that Gain’s data show significant decreases in GluSph even in idiopathic Parkinson’s (I could not find this information), this could slightly change the company’s operational window. However, it is still incorrect to say, as you did, that there is a suggestion from these data that a large number of idiopathic Parkinson’s cases have lysosomal lipid degradation failure as a primary or co-factor… I see only 4 cases, not the majority of the 10+ million Parkinson’s cases recorded worldwide, and therefore, if you cite these as exceptional data, forgive me if I did the same with what I reported above. In conclusion, if GT does not show concrete potential for idiopathic Parkinson’s, it will then have to test its cards on GBA1. BIAL will present phase 2 data in about 3 months, allowing us to conclude the chain, connecting—or not—the increases in GCase functionality to improvement in lysosomal repair function. One cannot invest in BIAL, but are you sure you want to invest in a drug that in 3 months could have a competitor with the same functionalities but 2 years ahead?

Correct_Proposal_409

A couple of things. First, what is interesting about the above slide is that only 1 of the 7 patients who showed a big drop in GluSph is GBA1. 4 of them were idiopathic, and 2 were "other". So this suggest that a large number of idiopathic cases feature lysosomal lipid stress as a primary or contributing factor. Second, GT-02287 is not simply “stabilizing GCase”. The human data now show functional lysosomal repair (large GluSph reductions) with patient-level concordance to clinical improvement. That’s very different from prior GCase approaches that increased protein or activity without correcting toxic lipid accumulation or showing a clear clinical correlation. Regarding BIAL’s program: it is restricted to GBA1-PD, targets a narrower downstream mechanism, and has not shown GluSph reduction or a biomarker-to-clinical linkage like this. Being further along in development doesn’t help if the biology isn’t hitting a disease-relevant bottleneck. Many PD programs have reached Phase 2+ without demonstrating disease modification. Maybe I'm missing this promising data, but from what I've seen, even pre-clinically, it has not shown improvement in mitochondrial function, reduction in a-syn aggregation, reduced neuroinflammation, reduced ER stress. All of these were shown pre-clinically by GT-02287, and now this reduction in GluSph, along with linking it to UPDRS improvements, goes a long way towards validating these pre-clinical findings. Do you have a link to this promising Bial data?

MediumSinger8088

No price moves based on any data. Big players bet millions of $ and make money on a few cent moves. So buy on rumor / sell on news; any analysis is limited to an algo sensing initial price moves. Since Gain didn't cure PD all of a sudden and get FDA approval RTF now, there would be a drop. So long as it isn't 50% in 2 minutes directly after the PR release, it's just about as to be expected.

MediumSinger8088

Purely objective analysis of P3: With this N, nonparametric WIlcoxon ranked signs test, P=0.22; modest sized difference but insufficient N for formal significance at this time point. A significant effect requires longer time and/or larger N; and/or a placebo group. Time more important than N if assessing stabilization vs. worsening on the MDS-UPDRS scale. Median change is now -2.3. AI-assisted analysis of expectation values: Based on historical precedent for de novo PD patients on levadopa therapy, the 1-year expectation value for change in MDS-UPDRS is about +2.4 points or about +0.6 points in 90 days. The minimum clinically important difference (MCID) is about 3.25 points. So, assuming drug treatment was started in patients in the levadopa "on" state, the median change from historical expectation values is about -2.9 points. Getting close to the MCID but not there yet. Needs more time, more N, a placebo group - i.e. Phase 2 strongly justified. I am very impressed by how transparent Gain is with the data, FWIW.

jadezsherz

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Capable-Display-7907

Yes. Right now for colorectal cancer, starting another metastatic triple-negative breast cancer (and have Expanded Access for TNBC patients now). The colorectal cancer trial should be reporting whether the drug has elevated PD-L1 expression by mid to late February; that's the sign that previously untreatable cancers can now be treated with checkpoint inhibitors like Keytruda. (In the earlier small trial, 88% of the patients had elevated PD-L1 after being treated with Leronlimab. Every one of the patients that then got a checkpoint inhibitor is now alive, five years later. I.e., there is a good statistical likelihood that nearly 90 percent of patients who have what has been considered unsalvageable solid-tumor cancers can be saved.)

wiisports101

If Canadian side keeps getting contracts, total will continue to expand but I don’t see savanna becoming as big as PD or ensign

Correct_Proposal_409

Phase 1 trials are to make sure that a drug is safe and shows target engagement. Phase 2 trials test efficacy in a controlled setting, and when phase 2 trials fail, it is usually because: * there is insufficient CNS exposure * the target turns out not to be central to the actual disease biology, * they don’t have the right patients. The drug may work for a particular subset of patients, but the trial has been diluted by too many patients who have a different disease biology. Parkinson’s Disease is often called Parkinson’s Disease**s** because there are multiple different points of initial failure which ultimately turns into Parkinson’s. Different genetic mutations, and some might start with lysosomal dysfunction, while others might start with mitochondrial dysfunction. Or maybe neuroinflammation. This is still being researched. * they are measuring the wrong endpoints, * they don’t have the timing right (i.e., trial not long enough to show efficacy, or the initial benefits don’t sustain for the length of the trial). * the biomarkers move, but they don’t translate to clinical benefits Gain’s 1b trial, along with the extension, gives them a lot of valuable information which goes a long way towards derisking the phase 2. Many phase 1 trials do not go nearly as far as Gain went since the 1b measured many biomarkers, along with clinical symptoms. This is unusual. The first major hurdle towards proving efficacy was reducing GluSph, since it is both a direct measure of lysosomal dysfunction and also a driver of further dysfunction and cellular stress. By reducing it in such a short time period (90 days) means not only that there was sufficient CNS exposure. It also strongly suggests that the lysosme has regained lost functionality and that the cellular stress burden has been reduced. And based on what we know about Gaucher’s disease, this GluSph reduction is a central marker for disease control, and the parallel lysosomal recovery is the key driver for disease-modification. So the most important biomarker for efficacy is already there. And the UPDRS score improvements that they’ve already released suddenly look more credible. We should know more about further scores and biomarkers shortly, but it follows that if GluSph was reduced so thoroughly in such a short time, other important biomarkers which take longer to affect should show signs of improvement even by 90 days, and if there is broad biomarker improvement, this reliably predicts clinical improvements since they are so well-correlated. The other big advantage of the data they know have is that they can use that to inform the phase 2 set-up. They’ve already narrowed the focus for their phase 2, tightening inclusionary and exclusionary criteria for enrolling patients, and they can further adjust as data comes in from the extension. Same with outcome measures. [Here is their current phase 2 registration](https://clinicaltrials.gov/study/NCT07280299?tab=table) (which can be updated). One inclusionary criteria that stands out is “Positive SAA in CSF at Baseline” and another exclusionary criteria is “PD-associated LRRK2 pathogenic variant or other PD-associated genetic mutations other than GBA1.”  They now know that GT-02287 is more likely to move the needle from a biomarker perspective by screening this way, so this increases the likelihood of success. So to answer your question, based on what we now know, I think the chances for success in phase 2 are high. And if we get more biomarkers (like Complex I, Miro1, aggregated a-Syn, NFL) that are beginning to show improvements, and if the UPDRS scores that are not worsening-- and I think Gain will show this data between the KOL and the AD/PD conference in March-- then I think the chances for phase 2 success will be extremely high.

Correct_Proposal_409

Yes. I'm not saying that there are no more risks to market. There are many risks from the beginning of a drug's development all the way through until approval by FDA. But GT-02287 has cleared the most significant of the risks. They first did extensive pre-clinical studies that showed that the drug *should* work in humans. They basically showed that GT-02287 reversed Parkinon's in animals. Then they passed a significant test in the phase 1a with healthy volunteers showing that the drug was safe, crossed the blood brain barrier, and achieved its target (Gcase) as predicted by the pre-clinical models. Many drugs fail in one or more of these steps. Most recently, in the phase 1b, safety was further established, and it took a big step towards showing efficacy by reducing GluSph by 75-95%, which had never been done in Parkinson's patients. The improvements in the UPDRS motor scores that showed in October suddenly look like they weren't just random increases. This reduction in GluSph also makes it likely that further downstream, slower-moving biomarkers should also show improvement,,, and clinical symptoms as well. So through the lens of likelihood of a successful phase 2 study, and also through the lens of large pharamas looking to partner, GT-02287 has been derisked to where the answer is "yes". I also think that the drug is even further derisked if you narrow the patient target to GBA1 Parkinson's (\~10% of Parkinson's cases), which is originally what they were targeting-- dysfunctional Gcase caused by a genetic mutation. They've since realized that improving functional Gcase is also important in idiopathic cases as well, which represent the vast majority of PD cases. This is why I think the asymmetry is so rare here. The risk is now low for failure, especially in GBA1 cases, but the upside is enormous.

microcapreturns

They have funding through 2026. Warrants are what has been holding them back and they at least bring in cash. I see a deal way before any dilution and AD/PD conference coming in March makes me think they are selling it all.

Correct_Proposal_409

There is a [KOL event](https://gaintherapeutics.com/newsroom/press-releases/press-releases-2025/gain-therapeutics-to-host-virtual-kol-event-on-gt-02287-for-parkinsons-disease-2/) on January 6th where they will be presenting more data, but more importantly will have two of the top experts in the world to weigh in o on the results, especially the significance of the GluSph reduction, which has never been achieved in Parkinson's, and which in Gaucher's disease (as I mentioned above) is life-changing. Beyond the KOL event, they'll be at two conferences, including the JP Morgan conference, which is where a lot of deals get done. They'll likely partner or get acquired before phase 2. IND filing/acceptance, and the AD/PD conference in March where they'll have more data from the extension study. And more UPDRS data along the way-- this tracks any motor improvements (as seen in the interim data in October). This will also likely me discussed at the [KOL event](https://gaintherapeutics.com/newsroom/press-releases/press-releases-2025/gain-therapeutics-to-host-virtual-kol-event-on-gt-02287-for-parkinsons-disease-2/).

MediumSinger8088

Very similar situation here. There may be some leaks in Jan-Feb about Phase 2 studies, and the March AD/PD event likely will include new data; so any drop in share price during January should be more muted than the one we saw a couple weeks ago. I generally sell if there is a big pop into over-bought territory too soon. Otherwise I try to ride it out. Or sell if something convinces me that my thesis was wrong or got broken.

stayfun

PD?

Melonskal

How is it a PD? They have a revolutionary low cost launch system for small satelites in a era where the space industry is seeing more and more investment

microcapreturns

Great info. We should get the data we expected in Q4 and then extended data at AD/PD. Gain Therapeutics(GANX): Final countdown to Phase 1b data at January 6th KOL Event https://gaintherapeutics.wordpress.com/2025/12/20/gain-therapeuticsganx-final-countdown-to-phase-1b-data-at-january-6th-kol-event/ 

MediumSinger8088

Deep dive- Peter Landsbury, the KOL advising Gain, was the CSO of Lysosomal Therapeutics around 2018. That company had a compound LTI-291 that allosterically activates GCase, theoretically similar (but different from) GT-02287 which chaperones folding of the enzyme. Lysosomal and LTI-291 got acquired by BIAL, which is sponsoring a phase 2 trial of the drug now called BIA 28-6156 (pariceract) called the ACTIVATE study in PD. Last patient due to visit clinic in April 2026 and topline data expected Q2. Published data that LTI-291 (28 days, 40 patients) did not change GluCer in CSF or plasma but paradoxically increased the analyte in peripheral monocytes. No effect on MDS-UPDRS in this study. Take aways: IMO BIA 28-6156 is the closest competitor to GT-02287 but there are key differences and results from ACTIVATE may affect Gain price in ways that are illogical due to Mr. Market confusing the MOAs. Also GT-02287 seems to have done something unique in decreasing CSF GluSph. Note there is no data arguing glycosylsphingosine is a biomarker for PD progression but is a marker of target engagement which WILL bring some big pharma players into a conversation at least. There is some evidence that PD patients with elevated GluCer / SM are more prone to cognitive decline over 3 years, which indirectly speaks to cholinergic pathways involved in AD (there's that AD connection). It will take a long time to see this all play out. Years. Invest accordingly. And circling back: Listen to what Landsbury says in the KOL talk. He's probably the most informed guy in the world about this topic.

-_-Ebenezer-_-

Stumbled on this company while looking up pgm mining companies. If the ground there holds as much PT and PD they say, along with the nickel, we'll be sitting very nice. I think it's a safe bet that eventually we'll see a return even if ground only holds half of what they say.

Afraid_Couple_2387

JFC if that ain’t my ex-husband (any way you can throw Borderline PD in there?).

eggsforyou

It almost feels like an attempt to induce panic selling / stop losses. The news today combined with everything else means Gain likely has the best PD treatment ever made, and that’s just one potential use. Plus their work, patents, and AI platform now have validated value for creating additional compounds. It sucks seeing the drop, but the fundamentals are the same and the data was just more good news. Scaring people out of their position seems to be a common strategy.

tt12345x

Not to be *that guy* but the FBI is currently looking everywhere for an unknown murderer that took out an MIT Professor dealing with nuclear fusion. Local PD now think that same person is responsible for the murders at Brown University’s engineering building just a few miles away. And now this insanely corrupt and nonsensical merger pops up just a few days later Is none of this weird to anyone else?

Correct_Proposal_409

Very unfortunate market reaction to positive news which goes a long ways towards confirming that the drug is working. The PR was to conservative, and they are holding back additional data (possibly due to CDA with a pharma partner, or the are holding data for the KOL event and the AD/PD conference, not sure). Regarding the KOL event, it sounds like they will be reviewing additional data: “The event will also review biomarker results from the Phase 1b clinical study of GT-02287, demonstrating disease modifying potential in Parkinson’s disease patients with or without a GBA1 mutation.” I just wish they had put that as one of the top bullet points for the PR. I’m holding for buyout/partnership, which I think is more likely now. BTW, the BTIG analyst just came out with this note, and he agrees: “Readout Suggests GT-02287 is Activating GCase in the CNS. Additional Steps to Confirm it a PD Drug, but the Gain Approach Works. WHAT YOU SHOULD KNOW: We see the findings today serving as definitive evidence supporting GT-02287&#39;s ability to activate GCase in the brain. As a result, we see validation for the Gain approach and increased likelihood others will agree and look to partner other novel applications where allosteric modulation of enzyme deficiencies might benefit patients. The readout today measured the levels of GCase substrate, glucosylsphingosine (GluSph) in the CSF. The observed GluSph reductions in every patient that had elevated levels of this GCase substrate at trial start make it clear: GT-02287 increases the activity of its target enzyme. After 90 days of GT-02287 treatment, all individuals with elevated CSF GluSph experienced significant decreases.”

Correct_Proposal_409

I'm down a lot. Tough day. Honestly, if I didn't already own so much, I'd be buying here. Stepping back and setting emotions aside, the biomarker data from today only further validates the drug. I think the PR was unfortunately a little too light on data and perhaps more layman-friendly language regarding implications of the one (very important) biomarker that they featured in the PR. I believe there will be an interview soon (maybe tomorrow) and the KOL even on the 6th where we'll get some more information. I think there are positive reasons they help some info back, for example: CNA with potential partners, regulatory risk (in speaking on sense of smell in the PR), AD/PD in March which requires any presentations to be new data (so they are holding for that), waiting for more KOL analysis. Anyway, I'm holding. This drug is worth much more than current SP indicates, IMO.

MediumSinger8088

We'll have to wait until the AD/PD conference in March to get more granular information.

DeepFriedPerch

Pure BS. ICIs (which is what I assume you are attempting to reference) *target* PD-L1. If PD-L1 is not being expressed (which is the case in about 60% of solid tumors), ICIs cannot be used. ICIs are very effective when PD-L1 is being expressed. Leronlimab induces PD-L1 expression, giving the potential to greatly expand the ICI market. Leronlimab also, on its own, inhibits metastasis, making it potentially a great partner drug for ICIs.

Capable-Display-7907

Peer-reviewed paper forthcoming: 1600 patients, no SAEs. Safer than aspirin. And as I say, it's not about proving anything to the FDA: if the ongoing trial shows the PD-L1 is elevated in most patients (and in a trial of 28 patients, Leronlimab elevated PD-L1 for 88 %), that will mean that Leronlimab is suddenly making the vast majority of colorectal cancers treatable for the first time. At that point the bidding among BPs should begin for partnership or buyout. The trial has just started, and they should have readouts of PD-L1 elevation in a few months. It's not about proving anything to the FDA. Approval will be the buyer's task.

rogex2

"It sounds like you need to do some more in depth research and due diligence my friend" Self own much? Many chemo drugs do increase PD-L1 especially on tumors that are already hot but not enough on cold tumors to make adding ICI's a viable combination. Leronlimab turns cold tumors hot to the point that ICI's sans chemo are highly effective making chemo superfluous.

Capable-Display-7907

"Actual approvals" won't be necessary. If you understand what several of us have been saying about the game-changing MOA of Leronlimab, you realize that any company that makes an ICI (Checkpoint inhibitor) will be drooling as soon as Cytodyn demonstrates -- by raising the PD-L1 levels of tumors -- that a few doses of Leronlimab changes impossible to reach tumors to easy targets for an ICI. Any ICI. In colorectal alone, that will suddenly make 85 % of all tumors treatable with an ICI, as opposed to the 15 percent that now can be treated. This will be a bonanza for whichever company wins the bidding war to come.

BGFGiraffe

What Wax doesn’t include in the snake oil pitch is that most drugs that treat cancer increase PD-1L, the protein he’s alluding to. Nice of him to pump his own board and cult following though.

Capable-Display-7907

Sheen was a patient. It's not his company, and he doesn't seem to realize that the drug he took for HIV is now called Leronlimab, and has had remarkable results vs. solid tumor cancers. In one trial five women with the lethal triple-negative breast cancer, all on at least their third course of therapy, were given a full dose of Leronlimab and a checkpoint inhibitor (like Keytruda). Five years later, all five are alive, and three of them are cancer-free. That is stunning. Cytodyn is now doing a trial against colorectal cancer in which it believes Leronlimab will raise the tumor's PD-L1 expression -- thus making it a viable target for a checkpoint inhibitor, which up till now has had so little success against colorectal cancer that it isn't even part of standard of care. Look up "turning a tumor from cold to hot" -- that's what this trial will almost certainly prove Leronlimab can do. The drug fully occupies the CCR5 receptor, which is the key to many many diseases -- not just solid-tumor cancers.

MediumSinger8088

Neuroinflammation - it's a thing. Take a mouse that's been genetically modified to have PD or AD-like disease characteristics (I won't say disease, mice don't really get the same problems, they don't have all the same neurons) as they age. Now impose a moderate head trauma or shock their immune system directly and neuroinflammation kicks off, driven by brain-resident non-neuronal cells (glia, especially microglia). The hallmarks of pathology that should start manifesting months later, start manifesting in days - weeks. Often it seems human AD / PD is diagnosed when symptoms manifest a few months after a significant physical injury as well. Neuroinflammation may be a type of catalyst or drives rates of progression. Why is this so important now? COVID mucked up all our blood-brain barriers. There is growing evidence that multiple sclerosis relapse, new AD and PD have inflected upwards already in the post-COVID era. Something to watch in the coming years.

SaezDs

Bought in SNTI now it dipped too much for no reason should bounce back quick. PD this is not a long term hold

gotobett

[Press Release BioNTech and Bristol Myers Squibb Present First Global Phase 2 Data for PD-L1xVEGF-A Bispecific Antibody Pumitamig Showing Encouraging Efficacy in Advanced Triple-Negative Breast Cancer 9 December 2025](https://investors.biontech.de/news-releases/news-release-details/biontech-and-bristol-myers-squibb-present-first-global-phase-2?mobile=1)

degen_supreme

PD. Valuation in the drain. Hoping it gets taken out soon at whatever price. Conscious if I sell, the matrix overloads will decide to let it get taken out the next day.

ImaginationRoutine96

Honestly, the “placebo = dopamine surge” explanation sounds scientific on the surface, but it doesn’t really line up with what we’re seeing in this trial. Placebo dopamine effects in Parkinson’s are real, but they’re short-lived, like usually hours to a few days, and they tend to fade, not strengthen, over time. They also don’t restore smell, don’t improve multiple functions months after dosing, and definitely don’t line up with changes in lysosomal or mitochondrial biomarkers. What people are reporting with GANX showed up after 60–90 days, not right away, which is the opposite of a typical placebo timeline. The improvements clinicians mentioned such as better balance, tremors quieting down, and even smell returning, aren’t things dopamine placebo spikes can sustain. Smell loss in PD has nothing to do with dopamine; it’s tied to lysosomal dysfunction and misfolded proteins. That’s exactly the pathway GANX is targeting by restoring GCase activity and mitochondrial function. So when patients start improving months into treatment, that fits the biology of a drug that repairs cellular machinery, not a short-term psychological response. If all we had were a couple of hopeful anecdotes, I’d get the placebo caution. But when you combine the timing, the type of improvements, the consistency across multiple patients, and the fact that GANX already showed GCase and mitochondrial restoration in human volunteers and patient-derived cells, the placebo theory just stops making sense. A dopamine placebo can’t fix lysosomes, mitochondria, or long-term motor function, it fades too fast and doesn’t touch those systems at all. We still need the biomarker readout, and that’s exactly what will separate hype from reality. But based on what we know so far, the “it’s all dopamine placebo” explanation doesn’t really hold up. This pattern looks a lot more like a real biological effect than a fleeting psychological one.

Outrageous_West_1564

I am saying Gene is the CEO of a microcap company repeating what hopeful patients and enthusiastic clinicians told him in an unblinded setting. That is not science; that is Investor Relations. Of course he is going to highlight the positive stories. You said: "It's not just smell... it's balance, tremors and motor functions." Exactly. That reinforces the placebo theory; it doesn't disprove it. Parkinson's is a dopamine-deficiency disease. The placebo effect in PD works by triggering the brain's reward system to release endogenous dopamine. What does dopamine fix? Tremors, balance, rigidity, and gait. If a patient has a strong placebo response, all of those things improve simultaneously. It is not magic, and it is not unique to this drug. It is biology I am not saying the drug definitely doesn't work. I am saying that every single thing you listed—tremor reduction, better balance, subjective smell return—can be fully explained by the dopamine-loop of an open-label trial. That is why the FDA requires Phase 2. If you want to bet that these anecdotes are unique to GANX, that is your call, but history suggests caution.

Outrageous_West_1564

You asked for a reference study on neuron recovery? There isn’t one because no drug has ever reversed Parkinson’s in humans. That’s exactly the point. But we know basic neurobiology, for example from trauma patients after bad car accidents and others: structural repair (neuroplasticity/axonal regrowth) is a slow, biological process. If you take Levodopa, you improve in 30 minutes. That’s symptomatic. If you claim to repair mitochondrial function and clear aggregates (disease modification), that should take months or years to translate into motor benefits. Seeing a rapid jump in function at 90 days screams "symptomatic effect" (or placebo), not "neuron recovery." Regarding the extension and patient expectations: You are ignoring the most famous case in PD history—the **Bristol GDNF trial**.  In that trial, patients felt so much better they swore they were cured. They moved better. They had their lives back. When the trial ended, they and their families protested and petitioned to keep the infusion ports in their heads because they didn't want to lose the benefit. Result? It turned out the most vocal improvements were often in the placebo group or statistically insignificant compared to placebo. Patients stay in extensions because they feel better. I am not denying the GANX patients feel better. I am questioning WHY. Is it the molecule? Or is it the potent cocktail of hope, better medical care, and the dopamine reward system? Until you run a blinded control arm, you cannot answer that. History says betting against the placebo effect in PD is a losing trade.

optimalpooper

I don’t disagree that there should still be caution, cknowledging your point: everything important is still unproven • Many drugs in PD had great preclinical data and target engagement in humans (including venglustat, ambroxol, prasinezumab) and still failed to move clinical endpoints. • GT-02287 is only in Phase 1b; there is no randomized Phase 2/3 efficacy data yet. The field has a high failure rate, and mechanistic plausibility does not guarantee clinical success. Myself like many others is really bought into the science and not acknowledging some of the stark differences between what Gain is doing with their “mitochondria first” approach and the other mentioned is underrepresented in your analysis. No one in the current/previous Parkinson’s pipeline has really done exactly what Gain is doing (physics-heavy 3D platform tightly integrated with AI for discovery). I always have planned outs and have also been holding for quite some time. Anyone interested in the breakdown comparison can reference below. (Used AI to help simplify the summary): What’s potentially better about GT-02287’s science 1. Mechanism sits at a biologic “hub.” GCase deficiency links lipid metabolism, lysosomal stress, and α-syn accumulation. Fixing that one node could, in theory, influence multiple pathogenic processes at once. 2. Precision small-molecule design. GT-02287 isn’t a repurposed drug; it’s optimized for brain penetration, specific allosteric binding, and lysosomal function, based on 3D structural analysis of the protein (SEE-Tx®). 3. Broad applicability beyond GBA1-mutant PD. Because GCase activity is also reduced in idiopathic PD, Gain is deliberately studying with and without GBA1 mutations, which could widen the addressable patient pool if efficacy is shown. 4. Strong biomarker plan. The Phase 1b study is not just “does the drug look safe.” They’re explicitly measuring GCase modulation and substrate changes in CSF/plasma, which should give a clean read on whether the biology works in humans, even before larger efficacy trials. How GT-02287 is different from Venglustat: • Fixing the enzyme vs. turning down the faucet. • Venglustat: Tries to help by reducing substrate load but doesn’t correct misfolded GCase or restore its normal lysosomal function. • GT-02287: Directly stabilizes GCase and improves its trafficking and activity in lysosomes, aiming to normalize the enzyme itself. How GT-02287 is different from Ambroxol: • Rational design vs. repurposed drug. • Ambroxol was never designed for the brain or for PD; it has other pharmacology (e.g., effects on ion channels) and needs high doses to get robust CNS effects.  • GT-02287 was discovered with Gain’s SEE-Tx® computational platform to bind a specific allosteric pocket on GCase and is optimized for CNS penetration and GCase modulation.  • Allosteric STAR vs. mixed-mechanism chaperone. Ambroxol is essentially a “happy accident” GCase chaperone; GT-02287 is a Structurally Targeted Allosteric Regulator with a clearly mapped pocket and structure-activity relationship. • Program built around biomarkers from day 1. GT-02287’s Phase 1b trial is explicitly built around CSF and plasma biomarkers (GCase activity, lipid substrates, PD-adjacent markers) as key secondary endpoints, on top of safety.  How GT-02287 is different Prasinezumab (Roche/Prothena)/Cinpanemab (Biogen): • Upstream lysosome repair vs. downstream aggregate mopping. • mAbs are dealing with extracellular or interstitial α-syn; they do little for the intracellular lysosomal/ER stress and protein degradation defects that likely drive disease. • GT-02287 aims to repair lysosomal function at the enzyme level, indirectly reducing α-syn burden by making the cell’s own disposal system work better. 

ImaginationRoutine96

        Yeah, I saw your other post and this comment and it reads like someone that’s trying to save their book, most likely because you have a short position and are getting wrecked. Some of the info is flat-out wrong and misleading.  1. Claim: “N=1 PRKN, 1–3 point UPDRS = noise” We’re not dealing with just one PRKN patient anymore. Gain’s December corporate deck shows 21 patients enrolled and 9 patients with 90-day MDS-UPDRS data, with a mean improvement of about –4.6 points on Part II+III at Day 90, and no acute dopaminergic bump at Day 30. Multiple PD studies treat roughly a 3–5 point improvement on MDS-UPDRS Part III as clinically meaningful. So saying “1–3 points is indistinguishable from noise” doesn’t align with actual PD clinical standards. 2. Claim: “Placebo effect makes this meaningless” True, PD has a strong placebo effect, but the numbers are being exaggerated. Yes, some trials have seen up to 20–30 percent placebo improvement, but that is the extreme end. A meta-analysis of blinded PD trials shows the average placebo improvement is closer to around 4 UPDRS motor points. Also, the GANX Phase 1b pattern is the opposite of a classic placebo spike. There was no benefit at Day 30 but a growing improvement by Day 90 in patients already on stable PD meds. Placebo responses are usually front-loaded, not delayed.  And Gain is not presenting Phase 1b as proof of efficacy; it’s safety plus biomarker plus functional signal to justify a randomized Phase 2. 3. Claim: “Venglustat failed, so this will too” Comparing venglustat to GT-02287 is scientifically inaccurate. They are entirely different mechanisms: Venglustat is a GCS inhibitor. It lowers substrate synthesis upstream. It reached target engagement but failed in the MOVES-PD trial, showing no benefit and possibly worsening progression. [Sources: MOVES-PD trial results] GT-02287 is an allosteric modulator of GCase itself. It stabilizes the misfolded enzyme, restores lysosomal function, and importantly, repairs mitochondrial pathways. The 2025 Neuroscience poster on Gain Therapeutics website shows GT-02287 increases mitochondrial GCase, restores complex I activity in severe L444P patient-derived cells, improves mitochondrial membrane potential, reduces ROS and cytochrome-c release, and protects dopaminergic neurons in MPP+ models. Independent research in Nature Communications also confirms that GCase is imported into mitochondria and is essential for complex I stability, reinforcing the mitochondrial mechanism that Gain is targeting. 4. Claim: “Other PD drugs like alpha-syn antibodies failed, so this will too” This comparison also doesn’t hold. Prasinezumab and cinpanemab were extracellular alpha-syn antibodies given to patients already far into disease progression. Targeting downstream aggregates didn’t slow disease enough in those studies. GT-02287 is targeting an upstream, genetically validated mechanism (GBA1) that affects lysosomal and mitochondrial failure. It has shown: • Target engagement in humans (53 percent increase in GCase in healthy volunteers by Day 14). • Preclinical rescue in both GBA1-mutant and idiopathic PD models. People should always be cautious with early-phase biotech, but framing GANX as if it’s nothing more than a placebo blip or “another venglustat” isn’t supported by the actual biology or the updated clinical data. If you want to argue valuation or risk profile, that’s fair but the scientific claims you made don’t match the real sources.

DAKING567

Chinese PD

douggilmour93

$AMD # AMD's Lisa Su dismisses AI-bubble talk while it prepares taxed MI308 exports to China [https://www.digitimes.com/news/a20251205PD220/amd-lisa-su-ai-demand.html](https://www.digitimes.com/news/a20251205PD220/amd-lisa-su-ai-demand.html)

ImaginationRoutine96

Anyone who starts a comment with ‘I’m a scientist’ instead of talking about actual data is usually not one. Real scientists discuss mechanism, biomarkers, trial design, and the published biology, none of which you addressed here. GT-02287 isn’t limited to mutation carriers, the trial includes idiopathic PD, and the mechanism is upstream of both genetic and non-genetic forms. Your points don’t line up with how GCase biology actually works. Also, if you look at his other posts he brags about shorting reddit posters stocks. He jumps across different threads pretending he’s an expert to potentially short the stocks. He even brags on one how he’s gone from 2k-20k. If he’s a scientist my dog is a neurosurgeon. 

One_Carpet_984

I think the argument was that the GBA1 drug they are making might also be able to modified to treat other variants of PD, i think there was another post that went in depth about the process and how its def a possibility if this drug shows promise. I could be wrong but i think thinks what i read.

Born2Vanderbilt

I don't like their science. Their small molecule only targets the GBA1 gene mutants. "GBA1 gene mutations are a common genetic risk factor for Parkinson's Disease (PD), found in roughly 5-15% of all PD patients, but significantly higher in specific populations, reaching 15-30% in people of Ashkenazi Jewish (AJ) descent. These mutations, particularly in the heterozygous state, increase PD risk and often lead to earlier onset, faster progression, and more cognitive issues, with common variants like E326K and T369M being key contributors. " If the inclusion criteria in clinical trials includes enrolling patients with specific GBA1 mutation, goodluck trying to complete clinical trials let alone recruit patients. Hence, the money making potential is weak. If they have other drugs in pipeline, would be happy to review.

Master-Vanilla-5625

GANX might be leaving the station Data on potentially decease modifying parkinsons drug set to be announced in the coming weeks ATM-offering announced this weekend, stock dipped to 3; Has now recovered to VWAP of yesterday (>3.20), trading at >80% (!!) volume compared to first day after ATM-offering news Current market cap: 117M, take-overs of decease slowing PD drugs - billions Upside for decease modifying PD drug is HUGE Still, data has a small N, somewhat speculative, could disappoint

Wolvshammy

I hadn’t heard of Tunnel to Towers but I love this option as well. I don’t agree with Jon Stewart politically, but his speech in front of NYC government officials on behalf of NYFD/PD and all first responders was absolute top tier. Gave me goosebumps.

Correct_Proposal_409

Great summary. Just a couple minor clarifications. Looks like the current market cap is around 162M since fully diluted share count is ~50M. Still, a long way to go to what could be $1B acquisition price, maybe more. Regarding sense of smell returning, we don’t know how many reports there were from the patients, but it sounds like there were at least a few. Looking forward to finding out more about that in particular since ~95% of PD patients lose sense of smell, and it almost never randomly returns. So if 15-20% reported recovering sense of smell, this would be a big deal.

TinyFugue

Annnd the cops storm your house and you lose it all to civil forfeiture. Congrats on buying the local PD a new margarita machine.

Mister_Dink

I do not think the feds are going to have too hard a time finding a private individual who's trying to do this. He's going to walk into a refinery with 100k in nickels and ask them to process and extract the raw metal, and the refinery is going to call the feds. alternately, the feds look for any bank (or local grouping of banks) that's recently cashed out thousands of dollars exclusively in dimes. It might be feasible to "launder" your source of thousands of quarters by operating a laundry or vending machine Buisness. Anyone who's collecting nickels, specifically, in a quantity that matters is an absolute weirdo whod be remembered at any location they've sourced it. People wildly underestimate just how big of a trail they leave behind. The criminals who get away with stupid shit do so because the local PD is staffed by equally stupid cops. Once the Feds get involved, it requires a much more careful criminal to get away with anything.

supp0rtlife

In post PD1 setting Pembro+Ipi = 10-13% ORR Amtagvi = 30%+ ORR You do the simple math.

Correct_Proposal_409

It is phase 2 ready. Phase 1a did everything it was supposed to do, and then some by increasing Gcase by 53% in the volunteers. That was unexpectedly good. The interim data for the 1b, which was in October, showed a mean improvement in motor function. It's a small group, but the most exciting development in my opinion is that some of the patients reported regaining their sense of smell. The vast majority of PD patients lose their sense of smell, and those that do very rarely have any recovery of that sense. We should know more in the next couple of weeks, but if, say 20%, of the patients are reporting regaining their sense of smell, that would be a huge development. Phase 2 will almost certainly happen with a partner or with whatever pharma buys them. The question is how much will they pay. $1 billion would be a great deal for the first disease-modifying drug for Parkinson's.

DAKING567

It’s a PD

Correct_Proposal_409

I try to keep going back to the data and what we know since I question myself daily on whether, against biotech major odds, they in fact have the first disease-modifying PD drug in history.

bennylechien

Going all in. I am no expert in stocks, but I will invest in problem solvers. A drug reversing PD would be a blessing. Fingers crossed (and thank you for your thoughtful analysis.)

Correct_Proposal_409

This is really interesting to me and I've been thinking a lot about this lately. Pattern recognition is one of our most important cognitive tools for survival. We'd be dead without it. And I have the same red flags that pop up often about this treatment. But pattern recognition bias cuts both ways. In biotech (and elsewhere), "too perfect" is especially worrisome since 95% of drugs fail, and scientists tend to expect disappointment. So the red flags of "seems to good to be true" is natural, but is still pattern recognition bias. So as often as that red flag pops up, I go back to "what do I know"... a mental inventory of all of the pre-clinical data, the phase 1a with healthy volunteers, what the interim data shows, statements by the company, etc., And then I do a sort of mental recalculation of likelihood that this drug works with some combination of PD subpopulations. I also run use different AI platforms to analyze all of the data (much of which I manually upload-- studies, slides, etc), and have them run probabilities. For what it's worth, the conclusion that I always come back to-- and of course I could be wrong-- is that there is less than a 5% chance that this drug does not help any subpopulation of PD. If it only helps, say early disease GBA1 patients, that's worth more than the current market cap. That's the ground floor for me. But from the totality of what we know to date, it is much more likely (by my assessment) that it works for a much broader population than just early GBA1. What "works" means remains more difficult to forecast at this point. My guess is that some percentage of patients will experienced slowed progression when on 2287 for a year or more, some will stop progression, and some will reverse progression to some extent. I'm not under the illusion that this will be a cure-all for Parkinson's, although I think it has a fighting chance to effectively be a cure for some GBA-1 patients.

Correct_Proposal_409

I would just make the distinction that Gain will not just be measuring target engagement. That will be interesting, though: what will Gcase activity look like with the PD patients as compared to the healthy volunteers, and what will the two GBA1 patients show? Many of the other biomarkers that Gain will be measuring are causally (not casually in case some eyes read it that way) linked to the direction and severity of disease. A-synuclein is core to the pathology. From what I could find, 90% of all PD cases show Lewy bodies and Lewy neurites, made mostly of misfolded a-syn. If 2287 reduces a-synuclein and they are also showing improved motor and olfactory function, this would be a very high signal of disease modification. They'll also be measuring lysosomal restoration, ER stress, inflammation markers, mitochodrial complex I. These are all well-known prime suspects in disease progression and pathology, and are fairly consistent across subpopulations of PD. My take is that the big picture that the collective data paints will be what is really meaningful, much more than individual biomarkers, or the UPDRS scores alone, or even the smell recovery alone. If they are all moving in the same direction, that convergence will be the Eureka moment for Parkinson's.

Worldly-Buy-5874

* \~11M diagnosed worldwide today; projected 25M by 2050 (fastest-growing neurodegenerative disease). * Diagnosis is still symptom-based; by onset, \~40% of dopamine neurons already lost → millions more undiagnosed. * New α-synuclein seeding assays (pathology-based) are gaining acceptance. Most likely, diagnosis will be faster even without showing symptoms. Preventative care will be super important. * No approved disease-modifying therapy yet; all current treatments are symptomatic only. We are still using levodopa since 1960. * First safe & effective disease-modifying drug will capture massive market share (tens of billions) and likely block recruitment for competing trials (patients won’t risk placebo/delay). Key competitors targeting misfolded α-synuclein which almost all people with PD has it: 1. GT-02287 (Gain Therapeutics): First-in-class oral GCase activator, restores lysosomal function → reduces toxic α-syn. Phase 1 completed. 2. Prasinezumab (Roche/Prothena): Monoclonal antibody directly binding misfolded α-syn; already in Phase 3. Far ahead. 3. HER-096 (Herantis): Intranasal CDNF-related molecule; early data suggest potential restoration, not just slowing. Mechanisms differ but complementary. Possible future combination use (Gain + Roche synergy plausible; acquisition interest likely). **Bottom line:** Positive GT-02287 data would be huge. Regulatory wind is strongly behind the first proven safe disease-modifying therapy, potentially fast-track/accelerated approval highly probable. First-to-market wins by a huge margin. I have PD and I follow every clinical trials/drugs/experiments religiously.

Emergency_Ad_9324

Anyone else buy all the dips of Pager PD ..fell like its the limbo. how low can you go

MediumSinger8088

I don't know, but no test is 100% sensitive or specific; and everyone has better days and worse days. Early on there have to be fluctuations in any functional parameter. The baseline is short. There seems to be little published in the way of formal studies. I did find this: Neurosci Lett. 2010 Dec 17;486(3):166-70.  doi: 10.1016/j.neulet.2010.09.044. Epub 2010 Sep 19. # The course of olfactory deficits in patients with Parkinson's disease--a study based on psychophysical and electrophysiological measures [Thomas Meusel](https://pubmed.ncbi.nlm.nih.gov/?term=Meusel+T&cauthor_id=20858529) [^(1)](https://pubmed.ncbi.nlm.nih.gov/20858529/#full-view-affiliation-1), [Birgit Westermann](https://pubmed.ncbi.nlm.nih.gov/?term=Westermann+B&cauthor_id=20858529), [Peter Fuhr](https://pubmed.ncbi.nlm.nih.gov/?term=Fuhr+P&cauthor_id=20858529), [Thomas Hummel](https://pubmed.ncbi.nlm.nih.gov/?term=Hummel+T&cauthor_id=20858529), [Antje Welge-Lüssen](https://pubmed.ncbi.nlm.nih.gov/?term=Welge-L%C3%BCssen+A&cauthor_id=20858529) Affiliations Expand * PMID: **20858529** *   * DOI: [10.1016/j.neulet.2010.09.044](https://doi.org/10.1016/j.neulet.2010.09.044) # Abstract **Objectives:** Patients with Parkinson's disease (PD) commonly show olfactory deficits in the early stages of the disease. These deficits can be verified psychophysically or electrophysiologically using olfactory event-related potentials (OERP). While psychophysical olfactory function in PD patients can improve over time, the course of OERPs in PD has not yet been investigated. **Methods:** Olfactory function was investigated twice in 19 patients at 5-year intervals. Psychophysical tests included the "Sniffin' Sticks" test battery. In addition, OERPs were recorded in response to two odors on each side (phenyl-ethyl-alcohol: 40% (v/v), H(2)S, 6ppm). OERPs were evaluated regarding existence (yes/no). Average disease duration at follow-up was 9.0 years and the average Hoehn and Yahr score (disease stage) was 2.2. **Results:** Psychophysically, 1 patient was normosmic, 14 were hyposmic, and 4 were functionally anosmic at the initial visit. Re-examination revealed 1 normosmic, 9 hyposmic, and 8 functionally anosmic patients. Mean olfactory function decreased significantly in all patients. OERPs were initially existent in 3 out of 19 patients. At follow-up, OERPs were no longer present in these patients, but were detectable in 3 other patients. **Conclusions:** Overall, mean olfactory function decreased, although improvements were observed at the individual level. We confirmed previous findings regarding psychophysical follow-up results. Electrophysiological measures showed a pattern of fluctuation in olfactory function comparable to that of the psychophysical results. These fluctuations do not seem to predict the course of the disease. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Dangerous-Retard

Goddammit. Was gonna grab PD puts at the end of the day but decided to inverse myself. Shoulda just REversed myself the fuck outta there.

MediumSinger8088

[Decline of olfactory function in Parkinson's disease: A ten-year longitudinal study - PubMed](https://pubmed.ncbi.nlm.nih.gov/40383932/)"....When excluding patients with an MMSE score below 24, reflecting cognitive deficits that might interfere with olfactory test performance, UPSIT score still decreased by almost 7 points over the follow-up period. Conclusions: Olfactory function in PD declines more rapidly with increasing disease duration than can be explained by aging or cognitive decline alone. As such, olfactory function appears to be a clinical marker of disease progression in PD that can be measured non-invasively and deserves consideration as part of multimodal phenotyping to monitor disease progression." Evidently there is a vetted test for this, and could be included in future trial design.

MediumSinger8088

The FDA has nuked numerous studies citing historical or external controls, which are only justified in cases of rare disease - muscular dystrophy, Huntington's (QURE recent debacle), etc. There are plenty of PD patients. For my part, if biomarkers show statistical significance (or even close in this small N), I will look for a strategic point to increase my exposure - just saying I hope the company plays by the book with the FDA.

MediumSinger8088

Caveats about biomarkers and their limitations: Novo Nordisk semaglutide failed in AD trials despite "positive" biomarker data - though the specific data was not disclosed, and stock tanked 6% (for a $200B company = 10 billion). Remember c. 2013 Lily's Segamacestat failed in AD despite very clear biomarker data for target engagement. AD-directed monoclonals approved largely based on biomarkers don't work and have risks. Biomarkers have value; certainly, if the target is validated (IMO amyloid in AD is NOT) and the markers show engagement that is reassuring. NFL and alpha synuclein in some forms of PD have meaning... but ultimately it'll have to be gold-standard placebo-controlled trials with objective clinical endpoints to prove disease modification in PD, AD or other major prevalent indications. IF that can happen - judging by NVO- the valuation would be worth many billions of dollars.

Correct_Proposal_409

My base-case is that this at least works for the GBA1 subpopulation, which would be worth multiples of Gain's current market cap. But all signs point to GT-02287 working for a wide range of PD patients.

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MediumSinger8088

Yes, this table summarizes clinical chemical variables that quantitatively separate early and intermediate-stage PD patients from matched normal controls. AI-assisted summary : Maybe a dozen PD trials report on-treatment biomarker effects of some sort. Most historically have not used biomarkers, report only baseline CSF, or don't collect CSF at all. Per ChatGPT 5.2: "If you restrict to: * **Phase 1–3 interventional drug trials in PD**, * with **published human data**, * showing **statistically or clearly described on-treatment changes in CSF biomarkers** that are: * either direct target-engagement (e.g., CSF α-syn, CSF LRRK2/pRab10, CSF GCase), * or mechanistically relevant inflammatory / neurodegeneration markers, then as of late **2025** the literature supports **roughly 7–12 distinct trials/programs worldwide** that meet this bar: * Inosine (SURE-PD) – urate * Ambroxol (AiM-PD + PDD trial) – GCase * Early nilotinib studies – HVA / protein markers (not replicated in NILO-PD) * Buntanetap – exploratory CSF panel changes * MEDI1341/TAK-341 – free CSF α-syn ↓ * BIIB094/ION859 – CSF LRRK2 & pRab10 ↓ + lysosomal proteins * VTX3232 – CSF IL-18 and related inflammatory markers ↓ * a small number of other GBA-, LRRK2- or α-syn-targeted early studies with limited or abstract-only CSF results." MEDI1341 is the most relevant and best results, but it is a monoclonal anti-alpha synuclein antibody being developed by Astra Zeneca and Takeda. Astra-Zen and Sanofi seem to be the biggest players with advanced programs in this area. Note one wants to find increased a-synuclein in therapy-receiving patient CSF, indicating the a-syn is being washed out of the brain.

Correct_Proposal_409

Well, with all the recent emphasis on α-synuclein in Gain’s posters and presentations, it wouldn’t surprise me if the internal data already show reductions in α-synuclein–related pathology. That’s been a consistent theme in their preclinical work. Regarding RT-QuIC — isn’t that mainly used to identify PD by detecting misfolded α-syn seeds, not to measure whether a therapy is repairing the underlying disease process (like reductions in α-syn aggregates)?

MediumSinger8088

Beware biomarkers. Correlation is not the same as causation. Some biomarkers are more likely related to etiology (causal basis than others). Among the possible markers being assayed, the alpha-synuclein is likely to be most important. The table below ranks the biomarker separation of PD vs. non-PD, in general (thanks ChatGPT... I generally agree with the summary). https://preview.redd.it/84wg7k1b9i2g1.png?width=1032&format=png&auto=webp&s=bc4706dfb303c4cb0a871c7cb5dfad66425af780

Careless-Sleep4527

Their Phase 1b trial is testing the drug "in people with PD with or without a GBA1 mutation" - so they're already exploring the broader opportunity. If it only works in GBA1 patients it'll be smaller market (\~$1-2B opportunity) but if the drug works for a larger group without GBA1 its a potential blockbuster (\~$10B+ opportunity)

stylebros

For real. The elites seemed to bought up shit housing stock as well. The burnt down house still sits there diminishing property value of the block. I asked my local PD who owns it as they do squatter checks there occasionally, and it's some company. They pay the property taxes so they're not in trouble, but the building is fully condemned. I don't get why they're holding a burnt husk or a house since 2021.

MediumSinger8088

Decent summary and comparison to Bial and Vanqua Bio: [Gain Therapeutics: Valuation Remains Low In Light Of Recently Reported Functional Improvement In PD Patients (NASDAQ:GANX) | Seeking Alpha](https://seekingalpha.com/article/4840077-gain-therapeutics-valuation-remains-low-in-light-of-recently-reported-functional-improvement-in-pd-patients)

MediumSinger8088

Interview about 10 minutes... Baseness asks what comes next "Is it partnership, is it going it to the clinic alone into Phase 2...." Mack says "If the data is there at the end of the year, it's choose your own adventure... we'll have spirited conversations about whether we want to go it alone with the cash we can raise...or a partnership... maybe a combination of those two things". One could imagine all kinds of way to divide the pie among indications (Gaucher's isn't being talked about nearly enough - I'm surprised they didn't go straight for this as a fast track to approval but chose to swing for the fences on PD).

Correct_Proposal_409

https://preview.redd.it/liydunxc5f1g1.jpeg?width=1284&format=pjpg&auto=webp&s=362b3c2f535995f3532c48efbe6ef92200e357a0 You’re right that dilution is common in biotech, and it in fact has been happening some via Gain’s ATM recently — but in Gain’s case it’s looking less and less likely that there will be a large, go-it-alone cash raise for P2. Gain has been in active discussions with a handful of mid- and large-cap pharmas for at least the last year, probably longer. Management has made it clear they do not want to run Phase 2 or Phase 3 alone, and these potential partners have already completed nearly all of their due diligence. At this point, the only missing piece is the biomarker data… and realistically, these companies either already have early access to it or will see it next week at Neuroscience behind closed doors. GT-02287 went into Phase 1b already mostly de-risked, with: • strong mechanistic clarity (ER → lysosome → mitochondrial rescue) • 53% GCase activity increase in healthy humans • full motor rescue in multiple animal models • dose-dependent reversal of α-syn and toxic lipids • safety and CNS penetration already proven The upcoming biomarker readout is essentially the final confirmation… no meaningful downside risk and enormous upside potential. Even (what I believe is) the base-case scenario (highly effective in GBA1 patients) is a multibillion-dollar market. Big pharma clearly does not necessarily wait for P2 anymore (see slide). If you’re Merck, AbbVie, Lilly, or Roche… why would you risk letting the first disease-modifying Parkinson’s drug in history slip to a competitor? Especially when: • 90%+ of PD patients have lysosomal / GCase pathway dysfunction • Early signals already include improved smell and balance — the rarest and strongest markers of disease modification • Gain’s market cap is \~$100M I this is exactly the point in development where large pharma steps in: after the biology is validated but before the price goes up 10×. Dilution is possible— but a partnership or acquisition is far more likely, and far more rational, given the competitive landscape and what’s at stake. Btw, they still have a significant amount of their ATM available, which they’ve been using strategically to add runway space.

MediumSinger8088

Biomarker data can't confirm reversal of pathology - by definition this must be done by postmortem histology or in some cases neuroimaging. Regarding olfaction, this is interesting. Evidently hyposmia or anosmia (loss of smell) occurs in 90% of idiopathic PD patients, early in the disease but isn't always reported. This feature seems to map to alpha synuclein accumulation in the olfactory lobe but not to dopaminergic cell loss ([Non-motor features of Parkinson disease - CORE Reader](https://core.ac.uk/reader/111018871?utm_source=linkout)), which gets around the argument that "dead dopaminergic neurons can't come back to life". If so, 02287 may indeed engage fundamental processes in clearance of protein aggregates that would suggest broader utility beyond PD.

Correct_Proposal_409

Thanks for the response. Any thoughts on how neurogenesis and neuroplasticity play into the equation, depending on the circuitry (and patient)? Theoretically, if a PD patient has lost most of their neurons in a given system, but the existing neurons recover function, that could create the right environment for neurogenesis, which once was thought to be possible only in young brains. Neuroplasticity could also support further recovery, similar to what is seen in stroke patients, where surviving neurons reorganized and take over lost functions.

MediumSinger8088

Correct. Of those 50% or so living neurons (really, judge histologically at death - say when a person who had PD died of a heart attack or something), they may only have 50% function. The degree of functional recovery is not known because, well, there's never been a way to functionally recover them in vivo in a human.

MediumSinger8088

The data on the poster is very transparent - with N=9, nonparametric stats, the median baseline on MDS-UPDRS part III (the objective physician evaluation) is 19 and 90 day change is -5; p = 0.14, which is not formally significant but indicates 14% probability of type 1 statistical error (saying there is a change when there isn't). So 86% chance of a treatment effect with this small N, early time. The anecdotal stuff is interesting but I want numbers - hopefully that will all be forthcoming. No risk, no reward. The real important thing IMO will be if there is a reduction in the rate of conversion to moderate or severe PD over 6, 12, 18 months based on MDS-UPDRS... and in a placebo-controlled study. It takes a lot of time to get a drug to clinic.

MediumSinger8088

Dogma is that, AT TIME OF DIAGNOSIS of PD, 50-70% of the dopaminergic neurons in the substantia nigra have died and 80% of dopaminergic function has been lost. Those aren't coming back. Now there may be restoration of function in remaining neurons, reduction in gliosis, non-dopaminergic things happening (cholinergic disinhibition of D1 pathways) etc that are more important and therapeutically addressable than previously thought. Importantly, GBA1 deficient patients seem to have earlier and greater cholinergic involvement. If this thing works textbooks will need to be re-written, med school curricula revised. Which would be very exciting.

ImaginationRoutine96

You’re framing this like Gain is clueless about whether the drug gets into the brain, but that shows you haven’t actually looked at the data. They already measured CNS penetration in humans in the Phase 1 MAD cohort. It’s right there in the deck. Healthy volunteers showed clear CSF exposure of GT-02287 — 3.1 ng/mL on average, which matches the levels that worked in rodent models. The rodents actually had 2–8x higher drug levels in actual brain tissue than plasma, which is exactly what you want for a CNS drug. So no, they’re NOT “waiting to find out” if it crosses the BBB. They already know it does. The upcoming readout isn’t about basic penetration; it’s about confirming that long-term dosing in Parkinson’s patients produces consistent CNS levels and that those levels tie into: GCase activation, lysosomal + mitochondrial restoration, sphingolipid reduction and alpha-synuclein-related biomarkers On top of that, they’ve already shown functional improvement by Day 90 in the Phase 1b group. That alone sets them apart from pretty much every symptomatic PD treatment and most early “disease-modifying” attempts. And yes, other companies are working on Parkinson’s. That’s not the point. AskBio’s gene therapy is a totally different approach which is invasive, risky, and expensive. GT-02287 is an oral small molecule that restores GCase function across the entire disease cascade. If you actually compare mechanisms, they aren’t even in the same category. So the idea that Gain is behind or “doesn’t know” whether the drug hits the brain is just wrong. They already proved CNS exposure. What they’re about to share is the translation whether that CNS exposure, in actual PD patients, lines up with biomarkers and functional benefit. That’s the data big pharma waits for before writing a check.

MediumSinger8088

The p-value for the MDS-UPDRS III data in the poster is 0.14 by non-parametric stats with N=9. So 86% chance of a real treatment effect, not formally significant but encouraging. Notably the placebo effect on phase 3 is small; typically about 1 pt or less (pretty objective); median baseline MDS-UPDRS was 19, median change at 90 days was -5. Real tell would be rate of conversion to moderate-severe PD at timepoints 6 months, 12 months, 18 months. There are 21 patients who will reach 90d in 12/2025 and will be followed for 9 more months so it shouldn't take long to see if the early stage results hold true.

MediumSinger8088

Typically in a severe progression if a drug has an effect it has it at some early-intermediate stage then loses efficacy. When a PD patient shows symptoms they've already lost 80% of their dopaminergic neurons. Those aren't coming back. If there is a persistent separation between placebo and control that increases in magnitude at 6, 12, 18 months... the textbooks will have to be re-written.

Correct_Proposal_409

I think you are right, if a little conservative. If I'm one of the handful of big pharmas-- say Merck, who doesn't want any of their competition to own the first disease modifying PD drug-- I might not mess around, knowing other bids will end up being much higher. A lowball would create bad will and distrust. I think one of the serious pharmas might come in big on the first offer in the hopes of making a strong first impression and building good will.

Responsible-Meringue

Jfc you're a fucking brick wall, if you're even human. I was asking you, since you know so much about the smell & PD clinical relationship. I know the answer to the first third, & we haven't discovered the last 2/3rds. I was at least cursoraly interesting in what you had to say. But you don't have anything to say.  Humanity is cooked. Your AI link is just an agent wrapper to the big providers foundation models. A 4 day old product with spurious claims at best, spun up from a PE acquisition when Edison Scientific went bankrupt 3 years ago. Literally AI circlejerk slop. Can't believe bot farms are pulling 13yo accounts now, and engaging in ways that are far too natural to quickly scrutinize. We are most definitely in dead Internet territory now.  

Correct_Proposal_409

You’re not wrong that an n of 9 in only 90 days can’t prove anything definitive by itself, but calling the data meaningless misses what this trial was designed to do. It was meant to see if the biology that worked in animals actually shows up in people. And it does look like it’s showing up. Biomarkers will confirm if this is the case, and it sounds like they will have that. The 4-to-5-point improvement on MDS-UPDRS after 90 days matters because untreated PD patients typically worsen 3–5 points per year. Seeing that direction reverse — and only start improving at 90 days, not 30 — fits a disease-modifying mechanism, not a placebo effect. A small change in part 2 is also positive since they didn’t feel worse after 3 months. Btw, the majority of the patients, and their clinicians, asked to be included in the 9 month extension. Why would they want another lumbar puncture and a nasty daily drink if they didn’t think it was working? Mean age was 63 and mean disease duration was 3 years. That’s not exactly cherry-picking. And the return of smell and balance in at least multiple patients is the opposite of noise. Over 90 % of PD patients lose smell permanently and spontaneous recovery is virtually nonexistent. When something that rare shows up in multiple patients on the same drug, it’s a pretty clean biological signal that α-syn pathology is being cleared. Obviously we need more data on that. What other Parkinson’s drugs that are not purely symptomatic showed full motor function recovery in animal models, made meaningful improvements in UPDRS pt 3 scores, and returned sense of smell in a significant number of PD patients? I haven’t found any. Tough crowd!

Responsible-Meringue

Everyones an armchair scientist now. Ill wait till you can describe how the molecular mechanisms of smell sensation are impaired by the loss of dopaminergic neurons in the substantia niagra and your hypothesis on how the likely MOA of this drug causes the restoration of smell, and how that is an direct indicator of  reversal of the PD pathology. 

Responsible-Meringue

Generalizing a single MOA across idiopathic disease of any kind is idiocy at best. Moreover, the read out of a single efficacy metric is n=9. Fucking 9, that's barely a study in an in-vitro clonal cell-line where literally evey replicate is assumed identical. Effect size is ridiculously small, only the observer half (pt3) of the MDS-UPDRS is changing... The patients themselves are reporting no change QoL from reduction in symptoms (pt2). I see the MDS-UPDRS results graph on their poster and immediately concluded "cool, to the outside world it looks like their motor issues are getting better, but they still feel like shit inside. This drug ain't working". Also asterisk the fuck out of the score scale too. The pt3 scores reported are on the lower fifth of disability ranges in PD trials (lower half of early onset however you want to define that bucket), and the delta is like 5. Of course this makes sense cause ph1 is safety/tolerability so they pick people with less-severe PD as to not interfere with AE reports.  I might bookmark this as something to check in on if pt2 had any change, but this readout doesn't pass the sniff test for promising or even surprising results.  AI is a really decent textbook, but you still need the years of scientific training & honing your critical thinking, and tempering your emotional bias to interpret data correctly. Honestly a AP science high-school student would do a better analysis. 

leadbetterthangold

My dad passed from PD and a smart investor friends told me about this one. I only own like 1,000 shares but have been in like a year or two. Mostly like that it reminds me of my pops.

Fabulous_Mission1070

ALL IN!!!lets double whammy improvements in life for PD patients and make some $$ what a gift

Correct_Proposal_409

BTW, it wasn't just a fluke. GT-02287 was designed to do exactly this, and they did a ton of pre-clinical work which also predicted that it should work in humans with PD. Every step along the way has been further confirmation that it works. The only surprises along the way were to the upside. For example, they were very confident it would work in the GBA1 subset, but weren't confident about idiopathic populations. Now they are seeing it helps both.

Additional-Rich-7216

Company Progress • The DOJ/SEC investigations are closed, and CYDY was not the focus of the case. • The company has treated over 1,600 patients and is submitting its safety profile and supporting data for publication. • The Phase 3 MDR-HIV trial achieved statistical significance. • The Phase 2 MSS-CRC trial builds upon promising basket-trial data showing tumor size reduction, modulation of the tumor microenvironment, and PD-L1 up-regulation—potentially enabling synergistic combinations with checkpoint inhibitors. Management has communicated that PD-L1 data is expected in January 2026, which could pave the way for partnership funding or collaboration opportunities. ⸻ Conclusion Given the company’s strengthened fundamentals, clinical progress, and the closing of its regulatory challenges, CYDY appears significantly undervalued at current levels. Based on peer comparisons alone, a near-term valuation in the $3–$5 per share range seems reasonable even before accounting for additional indications or future developments.

Additional-Rich-7216

Company Progress • The DOJ/SEC investigations are closed, and CYDY was not the focus of the case. • The company has treated over 1,600 patients and is submitting its safety profile and supporting data for publication. • The Phase 3 MDR-HIV trial achieved statistical significance. • The Phase 2 MSS-CRC trial builds upon promising basket-trial data showing tumor size reduction, modulation of the tumor microenvironment, and PD-L1 up-regulation—potentially enabling synergistic combinations with checkpoint inhibitors. Management has communicated that PD-L1 data is expected in January 2026, which could pave the way for partnership funding or collaboration opportunities. ⸻ Conclusion Given the company’s strengthened fundamentals, clinical progress, and the closing of its regulatory challenges, CYDY appears significantly undervalued at current levels. Based on peer comparisons alone, a near-term valuation in the $3–$5 per share range seems reasonable even before accounting for additional indications or future developments.

Additional-Rich-7216

Company Progress • The DOJ/SEC investigations are closed, and CYDY was not the focus of the case. • The company has treated over 1,600 patients and is submitting its safety profile and supporting data for publication. • The Phase 3 MDR-HIV trial achieved statistical significance. • The Phase 2 MSS-CRC trial builds upon promising basket-trial data showing tumor size reduction, modulation of the tumor microenvironment, and PD-L1 up-regulation—potentially enabling synergistic combinations with checkpoint inhibitors. Management has communicated that PD-L1 data is expected in January 2026, which could pave the way for partnership funding or collaboration opportunities. ⸻ Conclusion Given the company’s strengthened fundamentals, clinical progress, and the closing of its regulatory challenges, CYDY appears significantly undervalued at current levels. Based on peer comparisons alone, a near-term valuation in the $3–$5 per share range seems reasonable even before accounting for additional indications or future developments.

Additional-Rich-7216

Company Progress • The DOJ/SEC investigations are closed, and CYDY was not the focus of the case. • The company has treated over 1,600 patients and is submitting its safety profile and supporting data for publication. • The Phase 3 MDR-HIV trial achieved statistical significance. • The Phase 2 MSS-CRC trial builds upon promising basket-trial data showing tumor size reduction, modulation of the tumor microenvironment, and PD-L1 up-regulation—potentially enabling synergistic combinations with checkpoint inhibitors. Management has communicated that PD-L1 data is expected in January 2026, which could pave the way for partnership funding or collaboration opportunities. ⸻ Conclusion Given the company’s strengthened fundamentals, clinical progress, and the closing of its regulatory challenges, CYDY appears significantly undervalued at current levels. Based on peer comparisons alone, a near-term valuation in the $3–$5 per share range seems reasonable even before accounting for additional indications or future developments.

Additional-Rich-7216

Company Progress • The DOJ/SEC investigations are closed, and CYDY was not the focus of the case. • The company has treated over 1,600 patients and is submitting its safety profile and supporting data for publication. • The Phase 3 MDR-HIV trial achieved statistical significance. • The Phase 2 MSS-CRC trial builds upon promising basket-trial data showing tumor size reduction, modulation of the tumor microenvironment, and PD-L1 up-regulation—potentially enabling synergistic combinations with checkpoint inhibitors. Management has communicated that PD-L1 data is expected in January 2026, which could pave the way for partnership funding or collaboration opportunities. ⸻ Conclusion Given the company’s strengthened fundamentals, clinical progress, and the closing of its regulatory challenges, CYDY appears significantly undervalued at current levels. Based on peer comparisons alone, a near-term valuation in the $3–$5 per share range seems reasonable even before accounting for additional indications or future developments.

badinvesta

They also sell PD's as a service and then give those PD's shit information that leads to false arrests

0dteSPYFDs

It already has and UNH YTD stock price reflects that loss of goodwill. When you deal with indemnity for 3rd party BI&PD there are different expectations than with healthcare. You’re kind of shit out of luck if you get sick and your insurance provider tells you to kick rocks, but you also have healthcare advocates who fight for it. If you read more about what’s happened with tort reform in Florida it would give you a better picture of what would happen. Basically people were assigning their rights to sue to roofers. Those roofers would go through neighborhoods repair roofs after a storm, whether or not they needed to be or had existing damage that would have been denied by the insurer because insurance doesn’t cover wear and tear. In turn exchange for the right to collect from insurers property owners wouldn’t have to pay for the new roofs. Roofers would then go after their insurers for repayment, have to pay legal fees and punitive damages. Because of those jurisdictions being plaintiff friendly, they kept losing their pants in court, even when there was no bad-faith on their part. Basically a racket to extort insurers, but some of those loopholes have closed. You see the same types of problems with bodily injury from auto claims and billboard lawyers. Some places it’s the tort climate and others like southern Louisiana, it’s straight up collusion and fraud between claimants and personal injury attorneys. Long winded way of explaining it, but basically insurance for a lot of things is expensive, not because insurers have to pay for the losses, but because of frivolous litigation.