FVC

etaylormcp

[Study Details | NCT05415137 | Efficacy and Safety of Intravenous Efzofitimod in Patients With Pulmonary Sarcoidosis | ClinicalTrials.gov](https://www.clinicaltrials.gov/study/NCT05415137#study-plan) Look at the outcome measures |Outcome Measure|Measure Description|Time Frame| |:-|:-|:-| |Change from baseline in mean daily oral corticosteroid (OCS) dose at Week 48| |Baseline to Week 48| |Outcome Measure|Measure Description|Time Frame| |:-|:-|:-| |Change from baseline in KSQ-Lung score at Week 48| |Baseline to Week 48| |Steroid withdrawal rate| |Baseline to Week 48| |Change from baseline in absolute value of FVC at Week 48| |Baseline to Week 48|

Beneficial-Joke-7714

Please don't spread misinformation. There is no reliable evidence that efzofitimod was “outperformed by placebo” in the Phase 1b/2a trials. In fact, the published results suggest the opposite: efzofitimod showed signs of benefit compared to placebo, especially at the higher (“therapeutic”) doses. However, there may be some confusion or misinterpretation in media reports or summaries, so I’ll walk through the key data and why someone might mistakenly conclude the opposite. --- What the Phase 1b/2a Data Actually Show Here are the main findings from the trials in pulmonary sarcoidosis: The study was randomized, double-blind, placebo-controlled, with three dosage arms of efzofitimod (1.0, 3.0, 5.0 mg/kg) plus placebo. Efzofitimod was safe and well tolerated. There were no major safety signals. There was a dose-dependent improvement in several endpoints, for example: Steroid burden: people in the higher dose groups (3 & 5 mg/kg) had greater reductions in corticosteroid use than placebo or low-dose. Lung function (e.g. forced vital capacity, FVC) showed a trend of improvement in the higher dose arms compared to placebo or low dose. Some of those were statistically significant in post-hoc pooled analyses. Patient-reported outcomes (quality of life, symptoms) also showed improvements, especially at higher doses. One particularly strong result was a relapse rate during forced corticosteroid tapering: Among patients in the therapeutic group (3 & 5 mg/kg efzofitimod), only 7.7% relapsed after corticosteroid taper. In contrast, in the subtherapeutic group (1 mg/kg + placebo), 54.4% relapsed. Median time to first relapse in the subtherapeutic group ~126 days; in the therapeutic group nearly everyone avoided relapse for the 24-week duration. So, overall, the data support that efzofitimod at sufficient dose had better outcomes than placebo in several important respects. --- Why Some Articles Might Suggest “Placebo Outperformed” Given the data, why would there be articles saying placebo performed better, or that efzofitimod was “outperformed by placebo”? Here are a few possible reasons and misunderstandings: 1. Misreading “subtherapeutic” vs “placebo” groups The trial had a low dose (1 mg/kg), which was pooled with placebo in some analyses to form a subtherapeutic group. If someone misreads or conflates "low dose efzofitimod" with placebo, they might mistakenly think the drug arm underperformed. For example, a pooled analysis might compare therapeutic doses vs placebo + low dose (i.e. a group that includes placebo). If the subtherapeutic group includes patients on placebo and low dose drug, then raw outcomes might look mixed and someone might misinterpret those. 2. Not powered for efficacy in some comparisons The study was fairly small (37 patients), particularly when you split into multiple dose arms. Many endpoints, especially secondary/exploratory ones, did not reach formal statistical significance (or were only statistical in post-hoc analyses). Articles might highlight that uncertainty, or point out that for some endpoints the difference vs placebo was not statistically significant. This could be framed (either accurately or sensationally) as the drug “not beating placebo” or “no benefit over placebo” for certain outcomes. 3. Post-hoc analysis vs prespecified endpoints Some of the positive findings come from post-hoc pooled analyses (i.e. after the fact grouping of data, not in the original trial plan) rather than in every prespecified endpoint in each dose group. Post-hoc results are weaker evidence and more prone to bias or misinterpretation. Some critics may emphasize that. 4. Expectations vs magnitudes of effect Sometimes articles express disappointment not because placebo did better, but because the drug’s improvement was modest, or because people expected larger effects. If the improvements on lung function or quality of life were small or not consistent across all dose arms, some may say “it didn’t beat placebo convincingly” or similar. 5. Media or investor communication errors Press releases or media reports might unintentionally misstate or oversimplify. For example, they might say “no significant difference” when meant “no significant difference in some measures,” or “trend toward improvement” gets misinterpreted as “no improvement.” 6. Comparator group behavior Occasionally the placebo group shows better-than-expected performance (e.g. due to natural history, expectancy effects, maybe regression toward mean, patient selection) which can narrow the differences. If that happens, it might give the impression that the drug didn’t do much better than placebo, especially in subgroups. --- My Conclusion From the literature I reviewed: There’s strong evidence that therapeutic dose efzofitimod (3 & 5 mg/kg) outperformed placebo/low dose in key outcomes (relapse rate, steroid tapering, patient reported outcomes). There is no credible peer-reviewed evidence in these trials that placebo outperformed efzofitimod overall. Some endpoints didn’t reach statistical significance (especially in smaller arms or lower doses), but that’s not the same as being outperformed. It’s possible that some articles misstated results, took small-dose arms as “efzofitimod” vs placebo, or overinterpreted nonstatistically significant findings.

Connect_Cat_2045

These stocks have catalysts in September to October. September 8-10, 2025 (4-6 days from now): •  PSTV (Plus Therapeutics, $0.43): Presentation at H.C. Wainwright 27th Annual Global Investment Conference (September 8-10). Likely to highlight progress on CNSide, a cerebrospinal fluid diagnostic platform for detecting and managing central nervous system cancers (e.g., leptomeningeal metastases, ~$6B market). Positive data or partnership updates could drive 20-50% upside (~$0.52-0.65), based on historical conference-driven moves in micro-cap biotechs. Q3 2025 (by September 30) may also include updates on CNSide’s commercial launch or ReSPECT-GBM trial (rhenium-186 obisbemeda for glioblastoma), potentially adding 10-30% upside (~$0.47-0.56). Risk: Limited cash runway (~$8M market cap) and trial delays. •  September 10-17, 2025 (6-13 days): •  ATYR (aTyr Pharma, $5.44): Topline data from Phase 3 EFZO-FIT study for efzofitimod in pulmonary sarcoidosis (~200K US patients, no approved therapies). The largest-ever sarcoidosis trial (268 patients, 85 sites, 9 countries) tests steroid-sparing effects (primary endpoint: OCS dose reduction by week 48) and secondary endpoints (lung function, symptoms). Positive results could yield 200-400%+ upside ($16.32-27.20, ~$4406-7344 on 270 shares), potentially hitting your ~$5,000 goal at ~260% ($19.39, ~$5235). Negative results risk a ~50% drop (~$734). Confidence: 60-70%, based on Phase 1b/2a (58% steroid reduction, improved FVC), four positive DSMB reviews, and analyst Buy ratings ($17-35 targets). A late-breaker presentation at the European Respiratory Society (ERS) Congress (September 30, 2025, ALERT 3 session) may amplify visibility post-readout.  •  Throughout September 2025 (1-26 days): •  NRXP (NRx Pharmaceuticals, $2.60): Ongoing rollout of HOPE Therapeutics, including a flagship location in Palm Beach and advancement of ketamine-based treatments (NRX-100) for bipolar depression and suicidality (FDA Fast Track). No specific date, but updates on commercialization or trial progress could drive 10-30% upside (~$2.86-3.38). Less binary than ATYR’s data, but sentiment boosts possible given mental health market interest. Risk: Execution delays, funding needs (~$52M market cap).  •  September 29, 2025 (~25 days): •  IXHL (Incannex Healthcare, $0.66): Q2 or interim earnings report, potentially updating on cannabinoid/psychedelics trials (e.g., PsiGAD for anxiety, IHL-42X for sleep apnea). Positive trial updates could drive 10-30% upside (~$0.73-0.86), though earnings alone are less impactful unless paired with clinical milestones. Risk: Limited analyst coverage, high volatility (~$28M market cap).  •  September 30, 2025 (~26 days): •  FBIO (Fortress Biotech, $2.58): FDA PDUFA decision for CUTX-101 (copper histidinate) for Menkes disease, a rare genetic disorder (~1 in 100,000-300,000 male births). Priority Review, Breakthrough Therapy, Fast Track, and Orphan Drug designations signal strong data (80% mortality reduction, median survival 177.1 vs. 16.1 months). Approval could yield a Priority Review Voucher ($100M+ value) and 50-150%+ upside (~$3.87-6.45). Denial risks a sharp drop. Additional visibility from H.C. Wainwright conference (on-demand from September 5).  •  MBOT (Microbot Medical, ~$3.13): FDA 510(k) clearance decision for LIBERTY Endovascular Robotic System, expected by Q3 end (September 30). Pivotal ACCESS-PVI trial showed 100% navigation success, 92% radiation reduction, and no adverse events. Approval could drive 100-200%+ upside (~$6.26-9.39, based on $9 analyst target), enabling Q4 2025 commercialization. Denial risks a ~50% drop. Recent executive hires and $630K grant add sentiment. Risk: Regulatory uncertainty (~$20-30M market cap).  •  NVNI (Nvni Group, $0.586): H1 2025 earnings and investor webinar, with potential 1-2 acquisition closes by Q3 end. Strong revenue or AI/acquisition updates could drive 10-30% upside (~$0.64-0.76). Risk: Micro-cap illiquidity, Nasdaq compliance issues (~$21M market cap).  •  No Specific September Catalysts: •  ONDS (Ondas Holdings, ~$5.46): Recent stock offering (August 2025) and drone tech growth updates, but no confirmed September events. Q3 earnings (likely October-November) could drive 10-20% (~$5.57-6.55). Risk: Recent downside forecasts (-12% analyst target).  •  AIRE (reAlpha Tech, ~$0.39): Possible conference (e.g., H.C. Wainwright, not confirmed), but no specific catalyst. Q2 earnings (August 2025) showed 1909% revenue growth, but dilutions cap upside (10-20%, ~$0.43-0.47). Risk: High short interest, compliance issues.  •  IBRX (ImmunityBio, ~$2.34): No September-specific events. Anktiva (immunotherapy) launch updates or H2 2025 data (e.g., bladder cancer trials) could drive 20-50% (~$2.81-3.51). Risk: Debt, larger cap (~$1.6B) tempers volatility.

Huge-Truck8207

For those wondering about approval odds: Efzofitimod is currently in a global Phase 3 trial (EFZO-FIT™). While the industry average success rate for Phase 3 is ~59%, Efzofitimod’s case stands out due to multiple risk-reducing factors: ✅ Statistically significant Phase 2 results (steroid reduction, FVC improvement, QoL) → +10% ✅ Passed 4 DSMB safety reviews without issues → +5% ✅ Fast Track + Orphan Drug designations → +5% ✅ No viable competitors (Namilumab discontinued) → +3~5% 📊 Estimated combined probability of approval: ~80–85% (Compare that to the <10% average for new drugs reaching final approval) This is why many investors see aTyr as seriously undervalued.

Better-Ad-2118

Thanks for the response—and I completely understand the instinct to push back on lofty valuation targets. But let’s walk through your points carefully because, respectfully, some key facts may shift the risk/reward framing. **1. “Valuation is not absurdly low—it reflects trial risk.”** True in principle—but the degree of discount here is extreme relative to peers with similar data maturity. - ATYR trades at a ~$300M market cap while entering **Q3 Phase 3 readout** for a rare disease with **zero FDA-approved competitors**. It has: - Statistically significant Phase 2a data (+180mL FVC, p = 0.035; 85% relapse reduction) *(ERJ Open Research, May 2025)*, - A fully enrolled, DSMB-validated 268-patient Phase 3 (EFZO-FIT) *(aTyr Corporate Update, May 2025)*, - A running FDA-sanctioned **Expanded Access Program** based on investigator demand *(aTyr Q1 2025 earnings)*, - **Orphan + Fast Track** designation from both FDA and EMA for sarcoidosis and SSc-ILD *(FDA/EMA designations via aTyr IR website)*. This is not a preclinical pipe dream. It’s a **de-risked, regulatory-aligned, pre-commercial setup**. By contrast, Arena ($6.7B), Receptos ($7.3B), and Karuna ($14B) all had Phase 2/3 immunology assets at time of takeout—but **none had the biological depth or platform optionality** that ATYR offers in fibrosis, ILD, and oncology *(comps: Pfizer, Celgene, BMS acquisition data)*. **2. “Weakish readout or delay would be a big issue as money runs out in Q4.”** Important concern—but it’s not accurate to say they’ll run out of money before the readout. - Cash balance as of Q1 2025 = **$78.8M** *(Q1 2025 10-Q filing)*, - Runway explicitly covers operations **through and beyond Phase 3 readout** in Q3 *(Q1 2025 earnings call)*. In addition, aTyr is eligible for additional milestone payments from their Japan partner **Kyorin**—with over **$155M in development and commercial milestones** remaining *(Kyorin partnership agreement via aTyr IR)*. **3. “The trial is just testing steroid reduction, not disease modification.”** This is a misunderstanding of both the **design** and **regulatory context**. Yes, the **primary endpoint is steroid reduction**—but: - That is **aligned with FDA guidance** and accepted as a valid clinical endpoint in sarcoidosis *(FDA/ATS/WASOG guidelines)*. - The trial also has **secondary endpoints** for **lung function (FVC), quality of life (KSQ-Lung)**, and **symptom burden** *(ClinicalTrials.gov EFZO-FIT entry)*. Importantly, the *prior* Phase 2a trial already showed **concurrent improvement** across all of these dimensions—even during a forced steroid taper: - +180mL FVC - 85% reduction in relapse - Better KSQ and biomarker profiles than placebo *(ERJ Open Research, 2025)* And this isn’t just internal data: it’s **peer-reviewed, published**, and was even selected for the **Best of CHEST 2024** conference *(CHEST 2024 Abstract Highlights)*. **4. “This isn’t a multi-billion platform. That’s retail hopium.”** Again, let’s look at the facts: - **Sarcoidosis** TAM = $1.6B–$2.3B *(DelveInsight and GlobalData reports)*, - **Systemic sclerosis-ILD** = high-mortality, no curative options. TAM easily exceeds $1B *(Science Translational Medicine 2025; ACR/NIH estimates)*, - **CTD-ILD, CHP** and other ILDs = follow-ons with demonstrated NRP2 macrophage involvement *(Science Translational Medicine 2025; aTyr pipeline)*, - **ATYR0101**: Anti-fibrotic fusion protein targeting LTBP1 → $3B+ across liver, kidney, and lung fibrosis *(aTyr pipeline briefing, 2024)*, - **ATYR2810**: Oncology bispecific targeting NRP2/VEGF-C → data presented at **AACR 2025** *(AACR 2025 Abstract Book)*. Together, this forms a **tRNA synthetase-derived immunobiology platform with over 200 granted patents** *(aTyr IP portfolio overview)*. **Bottom Line** There are always risks in biotech, but $ATYR is being valued like a Phase 1 single-pathway flyer. That simply doesn’t match the dataset, pipeline, or strategic positioning. - This is a **Phase 3 platform** with clean safety, validated mechanism (NRP2), and FDA-aligned endpoints. - It is trading at **1/10th–1/20th the valuation of peer takeouts** with similar or inferior data. - Float is **tightly held by institutions (~97% of float), short interest is 12%, and volume remains thin**—all preconditions for structural dislocation if results are clean. No hopium here—just asymmetric math and a very real shot at re-rating. Appreciate the skepticism—it sharpens the argument. But this setup is rare, and all the ingredients are on the table. Let’s see what happens.

Better-Ad-2118

**Thanks for sharing your thoughts—there’s obviously value in discussing trial design concerns critically. That said, I believe several points in your comment fully deserve further clarification based on the EFZO-FIT trial design, published data, and best practices in steroid-sparing studies.** **1. Baseline Imbalance:** The claim that “the test groups were not identical at the start” doesn’t align with the published EFZO-FIT design (ATS 2024 abstract) or company disclosures. Patients were randomized across 85 global sites with strict eligibility criteria: biopsy-confirmed sarcoidosis ≥6 months, FVC ≥50%, KSQ-Lung ≤70, and baseline prednisone dose between 7.5–25 mg/day. The use of stratified randomization and exclusion of patients on >1 immunosuppressant minimized variability. In fact, EFZO-FIT is considered one of the *most rigorously designed placebo-controlled trials ever run in this indication*. **2. Confidence Intervals and Early-Phase Data:** Yes, the earlier Phase 1b/2a study (n=37) had overlapping confidence intervals between 5mg/kg and placebo on some endpoints—but this is typical in small early-phase trials. What mattered was that efzofitimod showed dose-dependent improvement in both **steroid reduction** and **patient-reported outcomes** (PROs), which led to 5mg/kg being selected for Phase 3. The EFZO-FIT trial (n=264+) is powered to resolve those CI overlaps and detect statistical significance. There have been *no DSMB stoppages or amendments*—a key signal that efficacy or futility thresholds weren’t breached early. **3. Steroid Tapering and Subjectivity:** You’re right: steroid-sparing studies can introduce subjectivity due to physician judgment. But EFZO-FIT minimizes this risk through: - Forced taper protocol: Patients tapered between Day 15–85, reducing variability. - Fixed baseline steroid range: All patients began on a standard 7.5–25 mg/day dose. - Blinded review and centralized protocols. Moreover, the trial triangulates steroid tapering with **objective measures** (FVC) and **validated PROs** (KSQ-Lung, SGRQ). So while subjectivity exists, the design incorporates safeguards to extract a clinically and statistically meaningful signal. **4. Signs of Efficacy Are Real—and Consistent:** In the earlier study, 5mg/kg efzofitimod demonstrated: - **A reduction in corticosteroid use**, exceeding placebo. - Statistically significant and clinically meaningful **improvements in KSQ-Lung and SGRQ**. - Dose-dependent reduction in **inflammatory biomarkers** like IP-10 and TNF-α. These multi-domain improvements—objective, subjective, and biological—form a compelling foundation for the Phase 3 program. **Bottom Line:** It’s fair to be cautious—biotech investing demands it. But the claim that efzofitimod’s Phase 3 readout is likely to be “ambiguous” underestimates both the **trial’s power** and the **biological signal** already observed. EFZO-FIT is unusually well-constructed for a rare disease trial, and efzofitimod’s selective NRP2 modulation represents a truly novel mechanism supported by translational science from Scripps, Boston Children’s, and aTyr’s mechanistic publications. And let’s not forget: the institutional ownership base has grown dramatically over the past two quarters, and now includes **FMR, Vanguard, Point72, Goldman Sachs, BlackRock, Adage, Alyeska, and Logos**—not typical behavior for a “maybe” readout. Their analysts would’ve already weighed all of these exact risks. $ATYR

Better-Ad-2118

Thanks for your thoughtful reply—and first off, respect for being “real hard” in. You clearly care enough to think critically, which I rate highly. Let’s unpack your points systematically, because they’re valid to raise—but I think there’s a stronger case than you might realise once we zoom in on the specifics. 1. “Retail hasn’t arrived” — Is that just narrative? This isn’t just a throwaway line—it’s based on hard signals in the data: • Daily volume averages ~100–200k shares—for a float of ~32.7M, that’s thin. • The price rarely holds >$4.50, which sits right beneath major call gamma clusters (especially for 5/17 and 6/21 expiries). • Reddit, StockTwits, and FinTwit coverage remains nearly non-existent relative to microcaps with similar setups. This is not a GME-style meme crowd yet. • No major breakout candle since late 2023. Price action still governed by low-liquidity grinding. That’s what “retail hasn’t arrived” means. It’s not about absolutes—it’s about relative awareness and inflow. This still trades like a stock no one is watching, despite the late-stage asset and real pipeline. 2. “Market makers are suppressing price” — or just natural price mechanics? Fair to question, and to be clear: we’re not alleging conspiracy. But there are signs of mechanical pinning behavior that often coincide with institutional accumulation phases. • Gamma exposure (GEX) has been persistently negative across key strikes ($4.00, $5.00, $7.50), indicating dealers are short gamma and need to sell into strength as price rises. • Call volume and OI in deep OTM strikes (5–10–15) have increased, with LEAPS disproportionately stacked. This asymmetry mechanically pressures price toward max pain until hedging dynamics flip. • Dark pool volume remains >50% most days, based on FINRA TRF and off-exchange prints. That suggests algo-mediated accumulation or suppression, not natural retail trading. These aren’t accusations—they’re structural facts of how illiquid options-driven stocks behave when institutions are building exposure and market makers are net short gamma. 3. “Gamma squeeze impact is overhyped in small biotechs” True if the float is large and options OI is low. But in this case: • Short interest is 12.23% of float, with ~10.7 days to cover . • Options OI at May/June 5, 7.5, 10 strikes is significant relative to ADV. • Gamma exposure flips around $5, which coincides with LEAP hedging thresholds and dark pool volume drops. When price starts moving with volume, dealers must delta hedge, which can mechanically escalate the move—even in small caps. See ARDS (2021), RLAY, and VSTM for examples of micro-cap biotechs with small floats that moved violently due to options-based dislocations. 4. “You glossed over the risks” Absolutely fair. Let’s confront them: a) Phase 3 failure risk Always real. But efzofitimod has: • Peer-reviewed Phase 1b/2a results: +180mL FVC (p=0.035), 85% relapse reduction • Clean safety, no deaths, and no withdrawals due to adverse events • A running Expanded Access Program (EAP) before readout—a rare vote of confidence from FDA and clinical partners • Mechanistic validation published in Science Translational Medicine: NRP2 binds inflammatory macrophages and reprograms them to pro-resolving states This isn’t a black-box biotech praying for a signal. It’s a de-risked candidate with multiple converging confidence signals. b) Funding / dilution ATYR has adequate runway through Phase 3 readout. Japan progress payments come into play too. More funding will come—but after the value-inflecting catalyst, not before. Also worth noting: insiders are buying. Director Jane Gross purchased 3,750 shares on March 17, 2025—bringing her total to 9,750. Not a large amount in dollars, but symbolically important during a pre-readout period . c) Adoption risk Pulmonary sarcoidosis is a high-unmet-need market. The standard of care is steroids, which are toxic and non-curative. There is no FDA-approved disease-modifying therapy. If efzofitimod gets approved with even modest payer support, uptake could be swift—especially since many patients are already on it via EAP or compassionate use channels. 5. So what’s the core disagreement? It comes down to how you weigh the coiled structure: • Float is small (~32.7M), with >12% short and heavy institutional ownership • Valuation is absurdly low ($300M) vs $500M–$700M rev potential in just sarcoidosis • Scientific, regulatory, and market signals are all aligning • Options chain and volume profile reflect a classic pre-breakout structure This isn’t hype—it’s an asymmetric setup where fundamentals, market structure, and psychology are beginning to converge. Happy to debate any of this, but I hope the added facts help clarify where I’m coming from. There’s a whole lot more that I could add. I respect skepticism—especially in biotech. But this setup is rare, and all the ingredients are in place. Let’s see what happens.

rurikrodion

It rallied up to that right before phase 3 result headlines, the data was readout from ALS FRS scores as I mentioned earlier an incredibly unreliable metric. Many enrollees were much sicker then previous trials so for their scores many started out as 0 for several functions thus couldn't reflect further loss of motor function and FVC breathing. The recent news before this rally was actually peer reviewed full trial data proving statistical significant improvements. Definitely do the DD and read the peer reviewed data before coming to any conclusions.

rustyperiscope

Bought the dip in FVC. One of their directors stepped down and somehow that impacted it.

strdlpopper

The fellow above who said he ran half marathons while smoking weed might be onto something. There are indications that smoking weed actually INCREASES lung capacity. To wit: It was previously thought that cannabis and tobacco had similar long-term effects as both cause chronic bronchitis. However, recent large studies have shown that, instead of reducing forced expiratory volume in 1 s and forced vital capacity (FVC), marijuana smoking is associated with increased FVC. The cause of this is unclear, but acute bronchodilator and anti-inflammatory effects of cannabis may be relevant. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072387/

academicpergatory

puts??F?V?EFV??VCD?FVC?SD?????!?!??!?!?!??!?!?!??!?! EXPIIRYYY WHAT STRIIKE PIUTUTTS PUTSSS>?????? PUTS???!?!?!??@?@?#?!!??