PD

Any_Pomegranate1134

**MGNX (MacroGenics, Inc.)** is a clinical-stage biopharmaceutical company focused on developing antibody-based therapeutics for cancer treatment. Recent developments include: * The FDA placed a **partial clinical hold** on the Phase 2 LINNET trial for lorigerlimab (a bispecific DART molecule targeting PD-1 and CTLA-4) in gynecologic cancers around late February 2026. This paused enrollment of new study participants. Some sources indicate the hold was later lifted, contributing to a recent stock gain (e.g., up \~4% in one session)

microcapreturns

https://preview.redd.it/o6ukkb5q4ung1.jpeg?width=1439&format=pjpg&auto=webp&s=719486cc9cfded7c43b9fcf86cf16e2472267507 The DDC biomarker being shown at AD/PD will be conclusive since the company has stated it correlates with the statistically significant data presented to date on UPDRS. Can't argue with statistically significant data if you understand the science.

microcapreturns

I see. I agree AD/PD is a huge catalyst. The way you wrote it I thought you were saying a PR was needed. Obviously not when up 20% for a week with crashing markets.

MediumSinger8088

Catalysts are small events that trigger a bit of buying/selling at key times leading to algorithmic amplification to the upside or downside. The AD/PD conference has been anticipated for months by many of us. It is logical to anticipate a decent probability of data update in the ongoing study. Data are nearing statistical significance on part 3 so the situation is primed for a break to the upside or downside. It's curious that we have a surge when the general market is being pulled down. On the other hand, Gain seems to trade like a software-as-a-service-stock, mirroring Nasdaq motion, rather than on fundamentals to the technology or industry specific trends.

microcapreturns

Great job. Stock should move up before AD/PD in a few weeks. Here was my recent article. https://www.reddit.com/r/pennystocks/s/mdUiShNRh4

eamus_catuli

In case you think the price of oil is going to stabilize soon. [Retired US Navy Admiral and former Supreme Commander of NATO](https://www.bloomberg.com/opinion/articles/2026-03-05/us-iran-conflict-tehran-can-make-the-persian-gulf-a-minefield?accessToken=eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJzb3VyY2UiOiJTdWJzY3JpYmVyR2lmdGVkQXJ0aWNsZSIsImlhdCI6MTc3MjcwODY2NiwiZXhwIjoxNzczMzEzNDY2LCJhcnRpY2xlSWQiOiJUQkVUVzVLSVAzSTgwMCIsImJjb25uZWN0SWQiOiIxODJBRTAzNUY2NDc0ODkwODhEM0VCRUVGRUUzQkJFMiJ9.wzma2PD5XIwUIq6pt6HvSB2mOpbUxcbLNisqSVLNwC8&leadSource=uverify%20wall): > Iran used mines four decades ago against Saddam Hussein’s Iraq. It has been planning a Strait of Hormuz closure operation for decades and probably has more than 5,000 mines; just one hit can severely damage a thin-skinned tanker. The Iranians can lay them covertly with small boats, diesel submarines and even civilian craft such as the ubiquitous dhows of the Gulf.

Icy-Bullfrog1891

Really looking forward to the AD/PD event. Really exciting time for Parkinson’s patients and Gain. Between this new biomarker data, and the new UPDRS data (I think Gene said we’d be getting that in a few months???), it’s just a matter of time.

microcapreturns

All it takes is convincing one big pharma that it works and a deal will get done. The DDC data will be huge at AD/PD.

proret4rd

PD ready to squeeze

proret4rd

All in on PD. Saas ain't done

microcapreturns

Look at Gain Therapeutics ($GANX). First small molecule drug that has been able to reverse Parkinson's and they present data in 2 weeks at AD/PD. Nobody has ever heard of them and these are in patient results. https://www.reddit.com/r/pennystocks/s/TscnH8yA9A

microcapreturns

GT-02287 is actually correcting the problem and will show data at AD/PD on how they repair dieing neurons. That's incredible news.

microcapreturns

Just read another published article yesterday showing DDC is an accurate biomarker for both PD and Lewy Body. Gains GT-02287 acts at the beginning of the problem and repairs neurons and reverses Parkinsons. Everybody else's drug works downstream and won't impact the DDC biomarker. It stands alone.

Correct_Proposal_409

I agree that GBA1 is the low hanging fruit. However, interestingly, only two of the high GluShp group were GBA1 (the only two GBA1 severe in the trial). The rest were idiopathic cases, which means that there are likely a large percentage of idiopathic cases with high GluSph. Since GluSph has only recently been able to be accurately measured in the CSF, this is something of a new discovery. One data point, but an important one. Since there is known association with and causation of dysfunction in various cellular areas (ER stress, a-syn aggregation, lysosomal & mitochondrial dysfunction), if all patients with high GluSph, regardless of genetic mutation, benefit from reduction in GluSph, this opens up the TAM by a large amount. GBA1 is somewhere in the 10-15% of PD cases, but perhaps 25-50+% of idiopathic cases either have or will develop high GluSph. The important thing is that this is not an obscure, downstream marker. This is an upstream, toxic lipid that feeds or possibly even initiates (i.e., GBA1 due to Gcase deficiency) the neurodegenerative doom loop.

R1ckMartel

You should really not hypothesize about things you have no knowledge of. Between PD-1 and PDL-1 alone, there are over ten available agents. Imfinzi has been FDA approved for almost a decade now. Its use is a fraction of Keytruda in clinical practice. It is not taking meaningful marketshare from Keytruda. Merck also recently had a subcutaneous Keytruda formulation approved, which will reduce chair time (not that Keytruda is bad at 30 minutes per infusion). When Keytruda's patent expires, a number of biosomilars will rush to market and that will hurt, but I don't think you have enough knowledge of the space to conjecture on immunotherapy.

Correct_Proposal_409

\~45% of the patients had high GluSph at baseline, and were then reduced by 81% to near normal levels. In those same patients, there was a statistically significant improvement in UPDRS (II/III combined) scores of 6.17 points in 90 days. Statistically significant. But this is not promising to you. What if they were to show DOPA decarboxylase drop in this same group? Sounds like they have this too based on the CEO's statements (to be revealed at AD/PD). I'd imagine they'll have plasma NfL soon in the extension patients. Bet you won't be impressed if that shows stabilization.

Correct_Proposal_409

So you have nothing to offer in terms of explaining why you think increasing the effectiveness of Gcase to reach multiple cellular compartments will not help a portion of PD patients. Got it. Not even in GBA1 patients, which have a mutation affecting Gcase. Lol. The share price is up from a year ago, so you have that wrong too. You know as well as I do that small many small biotechs have been hammered over the past couple of years. And you must not have much experience in investing if you think that markets get stocks right at every point in time. This is silly. My most successful investments have been in companies that have promise fundamentally but that had not yet been discovered by the general investing public. This is very common. This is called alpha. And you either know this and are being disingenuous or you simply are ignorant to this. Maybe your investment style is to buy well-known companies after everyone else has. You keep repeating the same "bagholder" line. My average cost is \~1.85. I'm doing fine, and don't need to offload anything. BTW, institutional ownership has gone up quite a bit, but still has a ways to go. https://preview.redd.it/lltd9ruaxolg1.png?width=1336&format=png&auto=webp&s=9ebe3455f67174db75e77d37d44496e030fb2c88

Correct_Proposal_409

You can use your own rhetorical "many trials have failed and therefore this is destined for failure" for any therapy being developed. Historical failure rates raise the bar, but they don't determine the outcome of a mechanistically unique therapy with a demonstrated CNS pathway correction. Here we have a genetically validated pathway (GBA1), plus strong evidence of Gcase dysfunction and corresponding lysosomal lipid accumulation in a good portion of idiopathic cases. If you are an MD, you should understand the relevance of GBA1 PD and Gaucher's-- they share the same GBA1 mutation. Life-saving, disease-modification was achieved by addressing dysfunctional Gcase, with GluSph being the most important biomarker for confirmation of target-engagement and disease progression. Of course, these Gaucher's therapies do not cross the blood-brain barrier. GT-02287 addresses dysfunctional Gcase in the brain. The reasonable take would be, "let's see how reducing GluSph levels translates to reduction in downstream biomarkers and in clinical symptoms in Parkinson's cases over a longer timeframe." Not, "I'll eat my shoes if this works". Hard to take you seriously when you are so seemingly dismissive without offering mechanistic reasoning to back up your statements. It almost seems as if you want it to fail. Do you work for a competitor of Gain? That would explain it. "Your post history is rabid with support of this stock... you are looking for someone to buy your bags." This is an immature, ad hominem assumption that does not address the science. Yes, I believe strongly in this treatment. I think it is the most promising PD treatment being developed, for the reasons I've detailed in my many posts. I'm lucky to have a very low basis. I *am* looking for BP to buy my shares for multiples above by basis. Not retail investors. I won't convince you-- not trying to convince you. But readers should understand that your baseless dismissal has no bearing on what many experts think is a very promising development in Parkinson's disease treatment. Maybe we should follow-up in September and see how durable the data is with the 16 out of 19 patients who elected to continue with the treatment despite the tests and additional lumbar puncture, many of whom have reported improvements, along with their clinicians. Beyond UPDRS, some of these reports may be anecdotal, but if they truly have regained sense of smell, this does not happen with placebo.

MediumSinger8088

Calling the shot Anybody can make a claim post-hoc. I'm posting expectations and we'll see if data is presented that substantiates the optimistic scenario. IMO the most relevant data is MDS-UPDRS part 3 (clinical evaluations) in the ongoing studies. Minimal clinically important difference is about 3.5 points. If the difference from reported - historical expected exceeds this, it's justification for confidence. By my tally last updated data was -3.1 before Christmas. If the AD/PD conference data shows the same or increased value, then Bayesian statistical interpretation favors "drug works". Basically take the 90 day expected MDS-UPDRS, double it, you get 1.26. Take the 180 day MDS-UPDRS difference from baseline. Subtract and assess the delta. It ain't rocket surgery. I'm calling my own personal criteria for continued investment before the data are released. NOT AFTER ... before. https://preview.redd.it/vtpqut3idklg1.png?width=1007&format=png&auto=webp&s=9b1c19db141517643f428bbc1dbb3c9288284dae

MediumSinger8088

Some time ago I posted my "play at home score sheet" with call-shots on MDS-UPDRS part 3 changes. When/if new updates are released in mid-march at the international AD/PD conference I'll update and post the progress.

Correct_Proposal_409

1. Karl Kieburtz, M.D., M.PH., and Kenneth Marek, M.D., two of the top experts in the world on Parkinson’s, lysosomal disorders, and neurodegenerative diseases would strongly disagree with you about GluSph. I doubt you’ll take the time, but you can watch them discuss the GluSph results here: [https://lifescievents.com/event/gst492thwp/](https://lifescievents.com/event/gst492thwp/) 2. Of course Gaucher’s is not Parkinson’s, but they share core overlaps in lysosomal dysfunction, in which GluSph plays a key role. There are plenty of papers out there. Here’s one on GluSph promoting a-syn pathology: [https://pmc.ncbi.nlm.nih.gov/articles/PMC5628407/](https://pmc.ncbi.nlm.nih.gov/articles/PMC5628407/)  Here’s another paper that discusses GluSph and Parkinson’s (and DLB): [https://www.nature.com/articles/s41531-024-00820-0](https://www.nature.com/articles/s41531-024-00820-0) 3. GluSph was prespecified for this trial by key opinion leaders and along with the FDA. GluSph reduction was one of, if not the top priority for biomarkers, since it means (1) that Gcase is doing its job effectively, and (2) because GluSph is known to cause a-syn aggregation, ER stress, lysosomal dysfunction, and mitochondrial dysfunction. You saying GluSph speculative is ignorance of the science and runs contrary to what the experts are saying. 4. The data was neither “heavily selected” nor anecdotal. You can’t fake GluSph reductions, and among that group, which is a large percentage of the patients, the UPDRS improvements are statistically significant. What is anecdotal at this point are the patients who reported improvements in their sense of smell and balance. Gain has added smell tests to the phase 2 so that this will no longer be anecdotal. 5. Liraglutide was an indirect metabolic approach. This is direct enzyme stabilization in a genetically validated pathway. 6. The links to the Reddit posts are my posts. These were all backed by research. Be skeptical, that’s healthy. But dismissing upstream lysosomal correction in PD as “speculative” ignores a large body of mechanistic literature.

Correct_Proposal_409

I don't think the market is pricing in any big reveals tomorrow. It cannot be viewed live, so we'll have to wait for a replay. But Gain continues to talk with partners. A deal will get done, the only questions are when and for how much. We'll get new data at AD/PD in a few weeks, and likely durability data from the extension at some point. My guess is that they've already shared the 180 day durability data (which they've not shared publicly yet). Maybe the word is getting out, and that's what we're seeing today. Plus some short covering. I continue to believe this is the most promising small cap biotech investment available today that most of the market still doesn't know exists. If the extension patients continue to show durable data, it's game on.

Correct_Proposal_409

Maybe we'll learn something new, or at least get some hints. We know there will be new data at AD/PD next month.

noahloveshiscats

Not really. [https://www.digitimes.com/news/a20260204PD210/market-dram-nand-cxmt-ddr4.html](https://www.digitimes.com/news/a20260204PD210/market-dram-nand-cxmt-ddr4.html)

Pipes255

OP backtested not even 4 years of data HA. In stats and backtests, 4 years is completely worthless. You’re gonna blow up like capn condor with these so called “stats”. Also, “very poorly” and “quite well” are not percentages. Back to the desk, back to work, get the true stats or be nothing. Here are some stats that matter. -98% of the time, one side of initial balance (IB) is broken. -95% of the time, one side of overnight (ON) range is tested. -83% of the time, one side of prior day range (PD) is broken. -80% of the time, the half gap (50% RTH gap) is tested. -55% of the time, the previous gap has been closed. -72% of the RTH days are Normal days (Bimodal/Trimodal). -18% of the RTH days are Trend days (Multimodal Profiles). -10% of the RTH days are Neutral days (Inside ON Range) Good luck out there degens!

Correct_Proposal_409

Take this for what it is worth, as you do not know me. I’ve spent a ton of time on this company and the data and the science over the last couple of years. While I was wrong about how the market would react to the phase 1b data, the data so far has been what was predicted by pre-clinical models and what science knows about Parkinson’s pathology, although this is still being sharpened. They have new data in hand, some of which is from the first 90 days of the 1b and which they’ll be sharing at AD/PD (and so it must be solid), and they also must have data from the first 90 day of the extension. All of their recent language tells me it is good. And this jives with recent direct and indirect communications with the company. Since the CEO made the statement about being more convinced each day that they have the first disease-modifying drug, he and the team have only become more confident. The problem with the price is that it is mostly retail-driven, and retail doesn’t understand the data or doesn’t have a long-enough attention span to stay invested. But this does not mean for a second that pharma partners are not interested and that they are not talking. They are talking. You are right that much of this will hinge on the “durability” of the data in the extension (i.e., does it continue to hold up over time). I strongly believe they already have some durability data as I said before. There’s no reason to think it won’t continue. I also believe that as-is, right now, a large pharma would pay 2-4X where we are now, and I’m sure there have been conversations, but the Gain team doesn’t think this is enough. I further believe that the bridge between what Gain wants and what BP is willing to pay is built with the durability data. So sometime before September, Gain will have this data, and they’ll be able to make a deal. Then the question is how much. I’ve stated many times that I think the deal that makes the most sense is a buyout with CVR. So cash up front, plus investors get to a CVR which they can cash in if the drug gets approves, and I think it will. Investors in this way will participate in the upside, and BP limits risk. I do not think the company will be sold for $200 million, unless the durability data isn’t very convincing. But there’s no reason to think it won’t be. It will not be a “fail”, that I am very confident in.

AdamN

I’ve been loading up on PD. A value stock with customer growth - nothing exotic but the type of thing that big companies keep even in hard times so slow and steady growth of large customers is a positive sign for me.

bobo-the-dodo

Chicago PD will enforce?

rvanasty

Different story just claimed she was released at the scene to local PD.

AmbivalentheAmbivert

Frankly what does local PD have to do with it realistically? Are you saying they need to comb the streets because the police are not cooperating? do they need to go after schools, court houses because police are not cooperating? It's a stupid comment, and realistically what does the average person have to do with it?

chickenpotpie25

Also local PD are working with ICE in these places.

Correct_Proposal_409

I did see that. Mack's quote is great because it very succinctly described how GT-02287 is superior than the other Gcase drugs, and also why (IMO) it is superior to the other treatments being developed which work around the edges by focusing on one cellular process or another. “Rather than simply trying to boost enzyme activity in the lysosome, GT-02287 stabilizes GCase folding and trafficking throughout the cell, restoring function across multiple compartments, including those critical to mitochondrial health,” Mack explained. “That matters because Parkinson’s can be seen as a disease of cellular stress, impaired waste clearance, and energy failure.” I could see a future where GT-02287 is a foundational treatment for many/most PD cases (and other diseases), while other downstream or peripheral treatments like the other ones mentioned are used in conjunction based on specific patient phenotypes or stage of progression.

I_Sniff_Uranus

City PD is a lot different than federal agents with “absolute immunity”

Cat_From_Jupiter

Holy fuck, Maegan out here being slutted out by an entire PD & getting paid $500,000 by taxpayers for it 😂. If this ain't winning Idk what is..

Honest-Muscle-7277

Swing trade in dave inc at 193 usd and hopefully the catalyst about its results I think it can make up bounce it to 220 - 240 usd. Stop 183 usd. I think that trump will not talk about regulations in fintech and based on its growth in eps, clients and revenue. PD: if someone knows the company or thinks another opinion i appreciate if you can reply my comment. Thanks

Correct_Proposal_409

As always, only invest what you are able to lose. That said, long term, I think this is the most promising and most de-risked disease-modifying treatment for PD that is being developed. I just don't know what the share price is going to do over the next few months at this point.

MediumSinger8088

Answering my own question... the standard of care for Gaucher's is enzyme replacement therapy, repeated injections every couple of weeks. For non-neuropathic Gaucher's you couldn't see a clear oral drug effect on top of the ERT and wouldn't get patients to forego the standard of care. Not enough market for neuropathic Gaucher's and if you're going to target CNS might as well go for PD.

MediumSinger8088

Many companies would go for the fast track in an orphan indication and hope to go for the big target after cash flow. Oh well. The only thing I can say is, my precious metals are making up for some of my "un"-Gain lately. Sorry I sold most miners prematurely but my explorer moon shots are doing OK and my real metals are... safe in a safe while we wait for March and the PD conference.

peenoiseAF___

I’m big on tracking catalyst events for biotechs and tools like tic⁤krbio make it way easier to track PD⁤UFA and clinical dates and see what could move a stock without digging through a dozen sites

Correct_Proposal_409

Yeah, I think it was simply that they felt confident in GBA1 Parkinson's, which is much bigger than the unaddressed neurologic Gaucher group. And proving disease modification in PD might open the door to Gaucher's more easily than the other way around.

MediumSinger8088

I have wondered why not prioritize Gauchers over PD. I just assumed it was a "swing for the fences" business decision, knowing that approval for PD would lead to off-label use and future expedited approval for Gaucher's.

MediumSinger8088

That's really interesting and suggests Parkinson's disease is more syndromic than previously appreciated. PD has always existed as part of a "Parkinsonian syndrome" with different presumed triggers but common symptoms. Perhaps there are metabolic subtypes of PD itself, some of which involve defects in lysosomal ceramide metabolism, and some that do not.

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.)