GRI Bio reports +99 mL FVC gain in Phase 2a IPF
GRI Bio, Inc. (GRI) reported new Phase 2a data for its lead IPF candidate GRI-0621, an oral RARβ/γ agonist, from the randomized, double-blind, placebo-controlled 12‑week GRI‑0621‑IPF‑02 study in 35 idiopathic pulmonary fibrosis patients.
Rhea-AI Filing Summary
GRI Bio, Inc. (GRI) reported new Phase 2a data for its lead IPF candidate GRI-0621, an oral RARβ/γ agonist, from the randomized, double-blind, placebo-controlled 12‑week GRI‑0621‑IPF‑02 study in 35 idiopathic pulmonary fibrosis patients. The study met its primary objective of safety and tolerability and generated translational biomarker and lung function signals.
Across four independent modalities (RNA sequencing, serum ECM biomarkers, spectral flow cytometry and clinical readouts), GRI-0621 showed direction‑consistent signals supporting nine mechanistic pillars, including immune re‑balancing, fibrolysis, basement‑membrane repair, re‑epithelialization, FVC stabilization, antitussive effect and GI protection. At Week 12, placebo‑adjusted FVC change from baseline was +99 mL overall and +139 mL on background standard antifibrotic therapy, with 39% of treated patients achieving an FVC increase ≥30 mL versus 20% on placebo and a 60% relative reduction in patients with ≥10% FVC decline.
GRI-0621 was well tolerated with no serious treatment‑emergent adverse events in the active arm, fewer cough, dyspnea and diarrhea events than placebo despite higher nintedanib use, and no hepatic, lipid, visual, auditory or neuropsychiatric safety signals. GRI Bio states that the totality of Phase 2a data supports advancing GRI‑0621 into a longer‑duration, 52‑week study.
Positive
- Exploratory FVC benefit: Placebo-adjusted FVC change at Week 12 was +99 mL overall and +139 mL on background antifibrotic therapy, with 39% vs 20% FVC responders (≥30 mL increase) and a 60% relative reduction in ≥10% FVC decline.
- Favorable safety and tolerability: No serious treatment-emergent adverse events occurred with GRI-0621 (0% vs 8% on placebo), with fewer cough (0% vs 25%), dyspnea (4% vs 17%) and diarrhea (17% vs 33%) despite higher background nintedanib use.
- Strong mechanistic support: Nine pre-specified mechanistic pillars were supported by direction-consistent signals from at least two of four independent modalities, including evidence of net fibrolysis, basement-membrane repair and alveolar re-epithelialization.
Negative
- None.
Filing Explained
The completed 12-week study adds biomarker evidence, but the next development stage is unfinished and requires substantial additional capital.
GRI Bio uses this Form 8-K to report completed 12-week Phase 2a findings for GRI-0621, including new biomarker results, while describing a longer study as the next step rather than a completed trial. The presentation also says the company’s current resources assume only initial preparation and that substantial additional capital would be required for a Phase 2b study, creating a disclosed future financing requirement without announcing a financing.
The filing calls the cross-modality results a defined mechanism and a positive FVC effect, but the study enrolled only 35 patients, treated FVC as an exploratory endpoint, and was not powered for efficacy; the new evidence therefore supports further evaluation without establishing a completed efficacy result.
As of
The named resolution path is a proposed 52-week evaluation of GRI-0621, including with background pirfenidone or nintedanib; the filing does not report that longer-duration study as completed.
Sources and calculations
- GRI Bio Form 8-K and Exhibits 99.1 and 99.2 (2026-09-08)
- Form 8-K purpose (current)
- GRI Bio latest quarterly fundamentals (2026Q2)
- Available liquidity against the last reported quarterly operating outflow, in days at that rate $10,947,000 / ($1,446,000 / 91) = 688.9 days
8-K Event Classification
3 items: 7.01, 8.01, 9.01
3 items
Item 7.01
Regulation FD Disclosure
Disclosure
Material non-public information disclosed under Regulation Fair Disclosure, often investor presentations or guidance.
Item 8.01
Other Events
Other
Voluntary disclosure of events the company deems important to shareholders but not covered by other items.
Item 9.01
Financial Statements and Exhibits
Exhibits
Financial statements, pro forma financial information, or exhibit attachments filed with this report.
Key Figures
Study size: 35 patients
Background antifibrotic use: 80% of patients
Placebo-adjusted FVC change overall: 99 mL
+5 more
8 metrics
Study size
35 patients
Randomized 2:1 in Phase 2a GRI-0621-IPF-02 (23 active, 12 placebo)
Background antifibrotic use
80% of patients
Participants on pirfenidone or nintedanib in GRI-0621-IPF-02
Placebo-adjusted FVC change overall
99 mL
Change from baseline at Week 12 for GRI-0621 vs placebo
Placebo-adjusted FVC change on SOC
139 mL
Change from baseline at Week 12 in background standard-of-care subset
FVC responder rate
39% vs 20%
Patients with FVC increase ≥30 mL, GRI-0621 vs placebo
FVC decline ≥10%
8% vs 20%
Patients with significant FVC decline, GRI-0621 vs placebo
Treatment-emergent diarrhea
17% vs 33%
Diarrhea incidence, GRI-0621 vs placebo over 12 weeks
Serious treatment-emergent AEs
0% vs 8%
Serious TEAEs in GRI-0621 arm vs placebo arm
Key Terms
idiopathic pulmonary fibrosis, forced vital capacity, spectral flow cytometry, retinoic acid receptor, +2 more
6 terms
idiopathic pulmonary fibrosis medical
"evaluating GRI-0621 (oral tazarotene) in patients with idiopathic pulmonary fibrosis"
Idiopathic pulmonary fibrosis is a chronic lung disease in which the air‑carrying tissue becomes progressively thickened and scarred for no identifiable reason, making the lungs stiff and less able to move oxygen—similar to a sponge that hardens and loses its pores. It matters to investors because it is life‑limiting with limited effective treatments, so clinical trial outcomes, regulatory approvals, pricing and reimbursement decisions can strongly affect the commercial value of therapies and the financial prospects of companies developing treatments.
forced vital capacity medical
"Approximately 2x–2.5x as many GRI-0621-treated patients experienced an FVC increase"
The amount of air a person can forcefully breathe out after taking the deepest breath possible; think of it as how much air you can squeeze out of a balloon in one hard blow. It matters to investors because it’s a common, objective measure used in clinical trials and patient monitoring for respiratory drugs, devices and treatments—changes in this number can signal whether a therapy works, affecting regulatory approval, sales and company value.
spectral flow cytometry technical
"28-color spectral flow cytometry of paired blood and bronchoalveolar lavage samples"
Spectral flow cytometry is a laboratory technique that analyzes individual cells or particles by capturing the full rainbow of light they emit when tagged with fluorescent markers, rather than measuring a few colors separately. For investors, it matters because it yields more accurate, detailed cell profiles—like upgrading from a limited-color photo to a high-resolution image—helping companies develop better diagnostics, targeted therapies, and faster drug-development decisions.
retinoic acid receptor medical
"oral retinoic acid receptor ("RAR") β/γ-selective agonist"
orphan drug designation regulatory
"Orphan drug designation delivers 7-yr US exclusivity from approval"
Orphan drug designation is a special status given to medicines developed to treat rare diseases affecting only a small number of people. This status often provides benefits like faster approval processes and financial incentives, making it more attractive for companies to develop these drugs. For investors, it signals potential for exclusive market rights and reduced competition, which can impact the drug’s profitability.
extracellular matrix biomarkers medical
"an expanded 12-marker serum extracellular matrix ("ECM") neo-epitope panel"
FAQ
AI-generated questions and answers. How Rhea-AI works. Not financial advice.
What did GRI Bio (GRI) announce regarding GRI-0621 in this 8-K?
GRI Bio reported new Phase 2a data for GRI-0621 in idiopathic pulmonary fibrosis, showing favorable safety, multi-modal biomarker signals across nine mechanistic pillars, and an exploratory +99 mL placebo-adjusted FVC gain overall and +139 mL on background antifibrotic therapy after 12 weeks.
How did GRI-0621 affect FVC in the Phase 2a IPF study?
At Week 12, placebo-adjusted FVC change from baseline was +99 mL overall and +139 mL in patients on background standard-of-care antifibrotics. 39% of GRI‑0621 patients had an FVC increase ≥30 mL vs 20% on placebo, with only 8% vs 20% experiencing ≥10% FVC decline.
What were the key safety findings for GRI-0621 in IPF?
GRI-0621 was well tolerated over 12 weeks: no serious treatment-emergent adverse events (0% vs 8% on placebo), no drug-related serious events, and fewer cough (0% vs 25%), dyspnea (4% vs 17%) and diarrhea (17% vs 33%) than placebo, with no hepatic, lipid, visual, auditory or neuropsychiatric safety signals.
How many patients were enrolled in the GRI-0621-IPF-02 study and how was it designed?
The Phase 2a GRI‑0621‑IPF‑02 study randomized 35 IPF patients 2:1 to GRI‑0621 4.5 mg once daily (n=23) or placebo (n=12) for 12 weeks. It was randomized, double-blind and placebo-controlled, with 80% of participants on background pirfenidone or nintedanib.
What mechanistic evidence did GRI Bio report for GRI-0621 in IPF?
GRI Bio reported nine mechanistic pillars supported by at least two modalities, including immune re-balancing, myofibroblast inhibition, fibrolysis, basement-membrane repair, re-epithelialization, FVC stabilization, and antitussive and GI-protective effects, with 18 of 72 RNA transcripts at FDR<0.05 and 13 flow cytometry readouts at p<0.05.
What are GRI Bio’s next steps for GRI-0621 based on these results?
GRI Bio states that the totality of Phase 2a data supports advancing GRI‑0621 in its IPF program and evaluating it in a 52-week study, including use with background pirfenidone or nintedanib. Further development will require additional capital or resources for a Phase 2b trial.
AI-generated analysis. How Rhea-AI works. Not financial advice.
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549 FORM 8-K
CURRENT REPORT
Pursuant to Section 13 OR 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): September 8, 2026
(Exact name of registrant as specified in its charter)
| (State or other jurisdiction | (Commission File Number) | (IRS Employer Identification No.) | ||||||||||||
| of incorporation) | ||||||||||||||
(Address of principal executive offices and zip code)
(619 ) 400-1170
(Registrant’s telephone number, including area code)
N/A
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
Securities registered pursuant to Section 12(b) of the Act:
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The Nasdaq Capital Market | ||||||||
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 or Rule 12b-2 of the Securities Exchange Act of 1934.
Emerging Growth Company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 7.01 Regulation FD
On September 8, 2026, GRI Bio, Inc. (the "Company") posted an updated corporate presentation to the Company's website at www.gribio.com/investors/events-presentations/ which is included as Exhibit 99.1 to this Current Report on Form 8-K. The information in this Item 7.01, including Exhibit 99.1, is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that Section, nor shall it be deemed incorporated by reference into any registration statement or other filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such filing.
Item 8.01 Other Events.
On September 8, 2026, the Company issued a press release announcing new translational biomarker data from the Phase 2a study evaluating GRI-0621 (oral tazarotene) in patients with idiopathic pulmonary fibrosis. The press release is attached as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated into this Item 8.01 by reference.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
| Exhibit No. | Description | |||||||
| 99.1 | GRI Bio, Inc. Corporate Presentation. | |||||||
| 99.2 | Press Release issued by GRI Bio, Inc., dated September 8, 2026. | |||||||
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). | |||||||
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Date: September 8, 2026 | GRI BIO, INC. | |||||||||||||
| By: | /s/ Leanne Kelly | |||||||||||||
| Name: | Leanne Kelly | |||||||||||||
| Title: | Chief Financial Officer | |||||||||||||
A New Approach to Inflammatory Diseases NASDAQ: GRI | gribio.com CORPORATE PRESENTATION SEPT 2026 Exhibit 99.1
Forward Looking Statements 2 This presentation is being presented by GRI Bio, Inc. ("GRI" or the "Company") and contains “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words such as “anticipate,” “believe,” “contemplate,” “could,” “estimate,” “expect,” “intend,” “seek,” “may,” “might,” “plan,” “potential,” “predict,” “presume”, “project,” “target,” “aim,” “should,” “will,” “would,” or the negative of these words or other similar expressions. These forward-looking statements are based on the Company’s current beliefs and expectations. Forward-looking statements include, but are not limited to, statements regarding: the Company’s expectations with respect to development and commercialization of the Company’s product candidates, the timing of initiation or completion of clinical trials and availability of resulting data, the Company's beliefs and expectations regarding preliminary data, the potential benefits and impact of the Company’s clinical trials and product candidates and any implication that the data or results observed in preclinical trials or earlier studies, topline or interim data or trials will be indicative of results of later studies or clinical trials or final data, that final data will be indicative of a proof-of-concept, the Company’s beliefs and expectations regarding potential shareholder value, its financial performance and future financial posit ion, and future financial performance, the Company’s beliefs about the timing and outcome of regulatory approvals and potential regulatory approval pathways, the Company’s expected future milestones, shareholder value, and the length of time the Company’s current resources will fund its planned operations (which current estimate assumes only initial preparatory activities for GRI-0621 as substantial additional capital or resources will be required to fund a Phase 2b clinical trial of GRI-0621). Actual results may differ from the forward-looking statements expressed by the Company in this presentation and consequently, you should not rely on these forward-looking statements as predictions of future events. These forward-looking statements are subject to inherent uncertainties, risks and assumptions that are difficult to predict, including, without limitation: (1) the inability to maintain the list ing of the Company’s common stock on The Nasdaq Capital Market and to comply with applicable list ing requirements; (2) changes in applicable laws or regulations; (3) the inability of the Company to raise financing in the future; (4) the success, cost and timing of the Company’s product development activities; (5) the inability of the Company to obtain and maintain regulatory clearance or approval for its respective products, and any related restrictions and limitations of any cleared or approved product; (6) the inability of the Company to identify, in-license or acquire additional technology; (7) the inability of the Company to compete with other companies currently marketing or engaged in the development of products and services that the Company is currently developing; (8) the size and growth potential of the markets for the Company’s products and services, and their respective ability to serve those markets, either alone or in partnership with others; (9) that later data or clinical trials may be inconsistent with or contrary to data and observations to date, including that later data may not indicate a proof-of-concept or patient benefit; (10) inaccuracy in the Company’s estimates regarding expenses, future revenue, capital requirements and needs for and the ability to obtain additional financing; (11) the Company’s ability to protect and enforce its intellectual property portfolio, including any newly issued patents and its ability to obtain any expected patent term extensions, adjustments, exclusivities or disclaimers; and (12) other risks and uncertainties indicated from time to time in the Company’s filings with the SEC, including the risks and uncertainties described in the “Risk Factors” section of the Company’s most recent Annual Report on Form 10-K filed with the SEC on January 30, 2026 and subsequently filed reports. Forward-looking statements contained in this announcement are made as of this date, and the Company undertakes no duty to update such information except as required under applicable law. This presentation includes information and statistics regarding market participants in the sectors in which GRI competes and other industry data which was obtained from third-party sources, including reports by market research firms and company filings. None of the information provided by third-party sources has been independently verified. This presentation may contain trademarks, service marks, trade names and copyrights of other companies, which are the property of their respective owners. The use or display of any third-party’s trademarks, service marks, trade names or products in this presentation is not intended to, and does not imply, a relationship with GRI, or an endorsement or sponsorship by GRI. Solely for convenience, the trademarks, service marks and trade names referred to in this presentation may appear without the ®, TM or SM symbols, but such references are not intended to indicate, in any way, that GRI will not assert, to the fullest extent under applicable law, their rights or the right of the applicable licensor to these trademarks, service marks and trade names. - NON CONFIDENTIAL -
GRI-0621 in IPF: a safety-led wedge into a $6-9B market 3 - NON CONFIDENTIAL - Adaptive Ph 2b/3 · orphan drug exclusivity + layered IP through late 2040s if new families grant $6-9B US branded IPF opportunity by 2035 AFT market growing 6-9% CAGR · US = 75% of branded revenue ~10% of US IPF patients on approved AFT today Closing just 1/3 of that gap = $5-9B incremental US TAM ~50% discontinue AFT within 12 mo (GI toxicity) GRI-0621: ↓ diarrhea signal vs SOC· antitussive · lung-repair biology M E C H A N I S M Concordant biology RARβ/γ agonism drives a coherent signature across transcriptomic (RNA- seq), proteomic (Nordic), cellular (spectral flow) and clinical (FVC, cough, dyspnea, diarrhea) readouts. Immune re-balance · fibrolysis · lung repair · anti-tussive · GI-protective I P + E X C L U S I V I T Y LOE runway Orphan drug designation delivers 7-yr US exclusivity from approval. Three new patent families filed in 2026 (SOC combination, antitussive, GI-protection). Baseline: late 2030s · If new IP grants: late 2040s R E G U L A T O R Y De-risked path ODD granted · FDA fee waivers · priority- review leverage · 1,700+ patient prior safety history from tazarotene topical use supporting oral pivotal. ODD · fee waivers · priority-review · 7-yr US exclusivity A D A P T I V E P 2 B / 3 Faster & cheaper Single adaptive Ph 2b/3 replaces sequential Ph 2b + Ph 3. Saves 12-24 months, ~150-200 subjects, and ~$50M in cost vs sequential studies.1 Adaptive design saves time and capital compared to sequential studies T h e G R I - 0 6 2 1 w e d g e Better safety keeps patients on therapy, concordant biology derisks the mechanism, ODD + layered IP protects the runway, and the adaptive Ph 2b/3 delivers pivotal data 16-24 months faster than sequential P2b+P3. 1 The adapt ive Phase 2b/3 study design described herein is a proposed protocol and remains subject to FDA agreement. Final study parameters , including sample size, endpoints, and interim analysis timing, may dif fer materially from those presented.
Program Pipeline: Targeting High-Value Indications Programs Class Indication Preclinical Phase 1 Phase 2 Phase 3 Status GRI-0621 RARβ/γ Agonist (oral tazarotene) Idiopathic Pulmonary Fibrosis (IPF) Positive Phase 2 across all endpoints Adaptive Pivotal study next step GRI-0803 dNKT Agonist Initial Focus: SPMS or LN (SLE) IND-Enabling and Phase 1 Program Expected to Advance in H1 2027 Library dNKT Agonists TBD Proprietary Library - Multiple Pipeline Expansion Opportunities Library consisting of 500+ Proprietary Compounds to Fuel a Growing Pipeline 4 - NON CONFIDENTIAL -
5 GRI-0621 (Oral Tazarotene) RARβ / RARγ Selective Agonist Target Indication: Idiopathic Pulmonary Fibrosis (IPF) Positive Phase 2a data Addresses Unmet Needs Orphan Drug Designation Highlights - NON CONFIDENTIAL -
IPF landscape gaps and how the top programs address them 6 - NON CONFIDENTIAL - G A P 1 Cough & QoL IPF cough drives quality-of-life burden that SOC doesn't touch and Tyvaso worsens. GRI-0621 ✓0% treatment-related cough vs 25% PBO Nintedanib ●Neutral — no antitussive signal Pirfenidone ●Neutral — no antitussive signal Tyvaso ✕Cough is the leading AE and QoL cost G A P 2 GI tolerability SOC and add-on nerandomilast stack GI AEs that drive dose reductions and D/Cs. GRI-0621 ✓17% diarrhea vs 33% PBO (IPF-02) despite higher nintedanib use in the active arm Admilparant ✓Clean Ph2 GI profile (LPA1) Nerandomilast ✕+ninted 18 mg: 61.8% diarrhea vs 26.6%; 12.9% diarrhea-driven D/C vs 1.2% Nintedanib ✕~62% diarrhea on label; +35 pt vs PBO G A P 3 Systemic safety Multiple late-stage assets carry hepatic, BP, or bleeding warnings. GRI-0621 ✓No hepatic, BP, DDI signal TDI01 ✓Selective ROCK2 — favorable safety window Admilparant ●Transient BP drops (LPA1) Nintedanib ●LFT monitoring; bleeding risk Rentosertib ✕15% hepatic tox in Ph2a G A P 4 Retention (low D/C) → large incremental TAM Real-world discontinuation erodes efficacy for SOC and combos; GRI- 0621 has zero drug-related D/C to date. GRI-0621 ✓No treatment-related D/C Nintedanib ✕Real-world: 29–35% retained at 12 mo (65–71% D/C); 21% D/C in EU cohort Nerandomilast ✕+ninted 18 mg: 21.3% AE- driven D/C vs 12.7% (nintedanib alone) Rentosertib ✕22% D/C in Ph2a (hepatic tox driver) Buloxibutid ✕23% drug-related withdrawal (AIR) G A P 5 MOA breadth / repair Current SOC and most Ph3 competitors slow decline but do not enable repair. GRI-0621 ✓+150% subjects with no FVC decline vs SOC; ↓ dyspnea; Basement membrane repair + AT1/AT2 repair; ROCK2 ↓ CAV1 ↑ Buloxibutid ✓AT2R vascular remodeling; ↓TGF-β1 57% TDI01 ●ROCK2 — vascular, immune, fibrotic dual action Nintedanib ●TKI antifibrotic — slows decline only Pirfenidone ●TGF-β pathway — slows decline only Sources: GRI-0621-IPF-02 topline · ALOFT-IPF NCT06003426 · FIBRONEER-IPF ATS 2025 · INCREASE-IPF USPI · GENESIS-IPF Nat Med · TDI01 Sino Ph3 update · Vicore ASPIRE deck · Podolanczuk 2023 Adv Ther 40(5):2038–50 · Kou 2024 Eur J Clin Pharmacol 80(10):1445–60 · Noor 2021 Adv Ther 38(1) :268–77 GRI-0621-IPF-02 observations address the top 5 gaps in the IPF therapeutic landscape No head-to-head clinical trials have been conducted comparing GRI-0621 to any of the agents listed above. Comparat ive data presented on this s lide are derived from separate clinical trials conducted under different protocols, in different patient populat ions, at dif ferent times, and with different endpoints, sample sizes, and durations of treatment. Cross -trial comparisons are inherently limited and should not be interpreted as demonstrating superiority, non-inferiority, or equivalence of GRI-0621 relative to any other agent. Competitor data are sourced from their respective Phase 2 or Phase 3 trials as cited
Concordant Signals Across Nine Mechanistic Pillars Spanning Transcriptomic, Proteomic, Physiologic & Symptomatic Signals Unique Profile Observed ✓ Safe & Well Tolerated ✓ Immune Re-balancing ✓ Antifibrotic ✓ Lung Repair Signals ✓ FVC Preservation ✓ Antitussive ✓ GI-Protective 7 GRI-0621 (oral tazarotene) Immune Re- balancing Reduced Lung Injury Myofibroblast Inhibition Fibrolysis BM Repair Re- Epithelialization FVC Stabilization Antitussive GI-Protection GRI-0621 RARβ / RARγ Selective Agonist - NON CONFIDENTIAL - RNA, FLOW RNA, SERUM, FLOW RNA, SERUM, FLOW RNA, SERUM RNA, SERUMRNA, PHYS PHYS, SYMP RNA, SYMP RNA, FLOW, SYMP RNA = RNAseq, SERUM = serum protein biomarkers, FLOW = spectral flow cytometry, PHYS = physiological readout, SYMP = symptoma tic readout Nine Mechanistic Pillars
GRI-0621-IPF-02: Study Design 8 Randomized, Double-Blind, Placebo-Controlled, 12-week Phase 2 Study GRI-0621 (tazarotene) 4.5 mg oral once daily DRUG & DOSE N=35 IPF patients 23 active : 12 placebo (2:1) POPULATION 80% on antifibrotic ~ 60% nintedanib ~ 20% pirfenidone BACKGROUND SOC 12-week treatment Completion: Q4 2025 DURATION PRIMARY ENDPOINT Safety & Tolerability (adverse events, clinical chemistry) SECONDARY ENDPOINT RNA-seq, Serum Protein Biomarkers Flow Cytometry EXPLORATORY ENDPOINT Pulmonary Function Testing (FVC change from baseline) ENROLLMENT 61 assessed for eligibility 35 enrolled (26 screen failures) 23 GRI-0621 | 12 Placebo 19 completed | 9 completed - NON CONFIDENTIAL -
GRI-0621-IPF-02: Study Treatment Related Adverse Events 9 GRI-0621-IPF-02 safety population (N=35) * Dry lips, dry skin, arthralgia and myalgia are retinoid class effects (Grade 1-2), transient, consistent with tazarotene safety database (>1,700 patients). Manageable with standard supportive care; no organ-threatening risks Adverse Event GRI-0621 (N=23) Placebo (N=12) Any Serious TEAEs Cough Dyspnea Diarrhea1 Weight loss Any AEs Grade ≥ 2 AEs Dry Lips * Dry Skin * Arthralgia * Myalgia * 0% 0% 4% 17% 0% 83% 17% 30% 22% 13% 13% 8% 25% 17% 33% 17% 17% 0% 0% 8% 0% 92% - NON CONFIDENTIAL - 1 ~50% reduction in diarrhea despite higher nintedanib use in active arm (70% vs 42%)
GRI-0621 - Positive Shifts in Collagen Remodeling Rates Observed 10 Fibrillar collagen (III/VI) remodeling rates shifted towards net ECM degradation & fibrolysis Network-forming collagen (IV) remodeling rate shifted towards net synthesis & alveolar basement membrane repair Only Program in IPF to Show Anti-Fibrotic, BM Repair and Re-Epithelialization Signals Confirmed at molecular level: ARG2 · F2R · MMP1 · NUPR1 · ACTA2 · HTR2A · ROCK2 ·MYL12A · TXND5C · E2F3 · SMAD7 · ADAMTS1 · COL1A2 · COL3A1 · COL6A2/3 · PLOD1 · CAV1 · CCN3 · COL17A1 · COL4A1/2 · LAMA3 · ALDH1A2 · AQP5 · CRB3 · DLK1 · EHF · NAPSA Serum protein biomarker data supported by RNA-seq, physiologic and symptomatic results PRO-C6/C6M NET FIBROLYSIS -14.0-unit PRO-C3/C3M NET FIBROLYSIS -13.6-unit PRO-C3/CTX-III NET FIBROLYSIS -16.0-unit - NON CONFIDENTIAL - PRO-C4/C4Ma3 NET REPAIR +13.6-unit Unit = PBO-adj Δ %CFB
GRI-0621-IPF-02: FVC Responders vs Decliners 11 ~2-2.5x as Many Subjects in the Active Arm Experienced an FVC Increase (≥ 30mL) & Almost 2/3rds Fewer Experienced a Significant FVC Decline vs Placebo - NON CONFIDENTIAL - GRI-0621 INCREASED FVC FROM BASELINE GRI-0621 (all subjects) GRI-0621 (+SOC) Placebo (±SOC) 8% 20%39% 50% 20% GRI-0621 (all subjects) Placebo (all subjects) GRI-0621 treatment ↑ FVC GRI-0621 treatment reduces FVC decline by 60% +95% +150%
GRI-0621-IPF-02: FVC Exploratory Endpoint 12 Exploratory endpoint – study not powered for efficacy; 12-week placebo-adjusted change from baseline +99 mL Overall (ITT) GRI-0621 vs Placebo vs expected 3-40 mL decline +139 mL SOC Combination Subset (pre-specified exploratory) Strongest & most consistent signal +89 mL SOC Post Hoc Subset (1-per-tail Winsorized; post-hoc sensitivity analysis) - NON CONFIDENTIAL - GRI-0621 INCREASED FVC CHANGE FROM BASELINE Supported by ↓76% decrease in symptomatic dyspnea (4% vs 17%) ↑ alveolar basement membrane repair signals (PRO-C4/C4Ma3 · COL4A1/2 · CAV1 · LAMA3) & markers of AT1/AT2 epithelial repair (ALDH1A2 · CAV1 · DLK1 · AQP5 · CRB3 · EHF)
Cross-modality concordance across nine mechanistic pillars 13 - NON CONFIDENTIAL - GRI-0621-IPF-02 Phase 2a, Week 12 · direction-consistent findings across four independent measurement modalities ↑ up-regulated ↓ down-regulated ⇅ directional shift Mechanistic pillar Spectral flow 28-color · BAL & PB RNA-seq whole-blood transcriptome Serum ECM neo-epitope + ratios Clinical / PRO FVC · symptoms · safety 1 Immune re-balancing ⇅ iNKT TCR Vα24Jα18 (PD) ↑ · CCR4 ↓ · IL-4 ↓ · IL-13 ↓ IL-17A ↓ · IL-22 ↓ · IFN-γ ↑ ALDH1A2 (PD) ↑ · CCR4 ↓ · IL4 ↓ · IL13 ↓ · FOLR2 ↓ · P2RY12 ↓ — — 2 Reduced lung injury ↑ HLA-DR ↑ on IM/AM (re- programming); BAL eosin. & neutrophil ↓ ↓ PI3 ↑ · ARG2 ↓ · TNFSF10 (TRAIL) ↓ · F2R ↓ · ↓ CPa9-HNE ↓ · ELP-3 ↓ · VICM ↓ (macrophage activation) — 3 Myofibroblast inhibition ↓ TGF-β1 ↓ · BAL IM/AM MØ ↓ ⇅ ROCK2 ↓ · ACTA2 ↓ · F2R ↓ · TXNDC5 ↓ ·E2F3 ↓ · SMAD7 ↓ · HTR2A ↓ · MYL12A ↓ · CCN3 ↑ PRO-C3 ↓ · PRO-C6 ↓ (Type III/VI collagen synthesis) — 4 Fibrolysis — ↓ ADAMTS1 ↓ · MMP1 ↓ · COL1A2 ↓ · COL3A1 ↓ · COL6A2/3 ↓ · PLOD1 ↓ C3M /CTX-III /C6M ↑ · PRO-C3/C3M ↓ · PRO-C3/CTX-III ↓ · PRO-C6/C6M ↓ — 5 Basement-membrane repair — ↑ CAV1 ↑ · LAMA3 ↑ · CCN3 ↑ · NUPR1 ↑ · COL4A1/2 ↑ · COL17A1 ↑ ⇅ PRO-C4 ↑ (Type IV BM synth) · C4Ma3 ↓ · PRO-C4/C4Ma3 ↑ (net repair ratio) — 6 Re-epithelialization (AT1/AT2) — ↑ ALDH1A2 ↑ · CAV1 ↑ · DLK1 ↑ · NAPSA ↑ · NUPR1 ↑ · AQP5↑ · CRB3 ↑ · EHF ↑ — FVC ↑ as epithelial-repair readout (+99 mL PBO-adj; +139 mL +SOC) 7 FVC stabilization — ↑ FVC responder ↑ 2-2.5x; ↓ 60% non-responder ; Dyspnea ↓ 76% (4% vs 17%) 8 Antitussive — TRPV1 ↓ · TRPA1 ↓ · HTR1B ↓ · TAC3 ↓ · CALCB ↓ · CAV1 ↑ — ↓ Treatment-related cough 0% vs 25% (within-study) 9 GI-protection ↓ ARG2 ↓ · CCR4 ↓ · MRC1 ↓ FGF2 ↑ · FGFR1/3 ↑ · FLT1/4 ↑ · VEGFA ↑ · PDGFA/B/C ↑ — ↓ Diarrhea ↓ ~50% (17% vs 33%) despite higher nintedanib use in active arm C L U S T E R IMMUNE · INJURY · MYOFIBROBLAST FIBROLYSIS · BM REPAIR · RE-EPITHEL. FVC · ANTITUSSIVE · GI-PROTECTION ALDH1A2 ↑ · AQP5 ↑ · COL4A1/2 ↑ · MMP1 ↓ · PMEPA1 ↑ ⇅ ⇅ ⇅ ↑ PRO-C4/C4Ma3 ↑ (net repair ratio) ↑ ⇅ iNKT TCR Vα24Jα18 ↑ (iNKT/CD1d serotonergic axis modulation) ⇅
GRI-0621 in Combination 14 - NON CONFIDENTIAL - No pharmacokinetic conflict · orthogonal MOA · additive favorable FVC signal observed in the +SOC cohorts — across approved SOC, near-term launches, and every emerging Phase 3 mechanism CURRENT & NEAR-TERM BACKBONES Nintedanib Approved SOC · ~65% of treated IPF TKI (PDGFR / FGFR / VEGFR) GRI-0621 Fit +139 mL SOC-subset (70% nintedanib background) · 17% diarrhea vs 33% pbo + SOC Pirfenidone Approved SOC · ~30% of treated IPF TGF-β / TNF-α inhibition GRI-0621 Fit No CYP1A2 / 2C9 conflict · covers the pirfenidone segment nerandomilast cannot Nerandomilast Approved Oct 2025 · PDE4B cAMP-mediated anti- inflammatory GRI-0621 Fit Orthogonal MOA — RARβ/γ retinoid immunomodulation · additive on TKI + PDE4B Tyvaso Inhaled · Ph3 · sNDA filing H2 2026 Prostacyclin analog (inhaled) GRI-0621 Fit Oral · addresses Tyvaso's 48% cough liability directly EMERGING PHASE 3 MECHANISMS — ORTHOGONAL IMMUNE + MATRIX AXIS NONE ADDRESS Admilparant (BMS-986278) Oral LPA1 antagonist · Ph3 ALOFT-IPF Fibroblast activation / vascular leak GRI-0621 Fit Oral · orthogonal matrix axis · no additive hypotension (vs 31% asymptomatic in Ph2) TDI01 (Tide / Sino) Oral ROCK2 inhibitor · Ph3 Angiocrine: vascular / immune GRI-0621 Fit Complementary immune axis - ROCK2 ↓ oral · no CYP conflict Buloxibutid (Vicore) Oral AT2R agonist · Ph3 ASPIRE AEC2 epithelial / alveolar repair GRI-0621 Fit Distinct fibrolytic lever — MMP-13 (bulox) + type III/VI turnover (0621) · both oral, GI- safe GRI-0621 COMBINES WITH EVERY CURRENT AND EMERGING IPF BACKBONE No head-to-head clinical trials have been conducted comparing GRI-0621 to any of the agents listed above. Comparat ive data prese nted on this s lide are derived from separate clinical trials conducted under dif ferent protocols, in different pat ient populations , at different times , and w ith dif ferent endpoints , sample sizes, and durations of treatment. Cross-trial comparisons are inherently limited and should not be interpreted as demonstrating superiority, non-inferiority, or equivalence of GRI-0621 relative to any other agent. GRI-0621 data are from a Phase 2a study (N=35; 12-week duration; exploratory FVC endpoint; study not powered for efficacy). Competitor data are sourced from their respective Phase 2 or Phase 3 trials as cited.
15 dNKT Agonists GRI-0803 & 500+ compound library targeting innate-like immunoregulatory T cells GRI-0803 Target Phase 1 in 2027 SPMS or LN (SLE) Validate bioanalytical methods Complete cGMP manufacturing Complete toxicology studies Steps Toward IND Filing - NON CONFIDENTIAL -
Progressive MS: The Unmet Need 16 Where current disease-modifying therapies fall short 0 DMTs for Non-Active SPMS No approved therapy for non-relapsing SPMS — the largest gap in MS ~16d Disability Postponed / Year Average benefit of ocrelizumab/siponimod in progressive MS; effect plateaus ~43% Non-Active PPMS Untreated Large share of progressive patients remain untreated or keep declining Progression independent of relapse activity (PIRA) is the dominant driver — and remains unaddressed Source: Mult Scler Relat Disord. 2021. Neurology & Therapy 2023, Frontiers Immunol 2025 (SPMS) - NON CONFIDENTIAL -
Mechanism-to-outcome in EAE Source: Maricic et al., J Immunol 2014, Jahng et al., J Exp Med 2004 Activated in periphery and CNS Activated dNKT cells are present in both the peripheral immune compartment and the CNS of EAE models Expand MDSCs; tolerize microglia Activated dNKT increase myeloid-derived suppressor cells and inhibit microglial activation markers (CD80/CD86, MHC II) Inhibit pathogenic T cells Suppress encephalitogenic Th1/Th17 IFN-γ and IL-17A secretion in periphery and block CNS infiltration Reduce clinical scores — treatment setting Activated dNKT lower EAE disease scores after onset and is effective with repeated weekly oral dosing MS Data: What dNKT Activation Does 17 - NON CONFIDENTIAL -
Key Takeaways: dNKT Agonists in SLE 18 NZBWF1 lupus model — selective, mechanism-driven activity Selective Not Broad Immunosuppression Inhibits iNKT, CD4, CD8 & B cells — but not neutrophils, eosinophils or monocytes ↓ LN Reduced Lupus Nephritis Lowers anti-DNA antibodies and TNF-α; blocks key signaling pathways dNKT agonists act as a targeted immune reset — not an unspecific immunosuppressant ↓Proteinuria Renal Protection & Survival ↓ proteinuria & ↑ proteinuria- free survival in NZBWF1 lupus —the principal predictor of progression to ESRD and mortality in SLE/LN - NON CONFIDENTIAL -
Intellectual Property & Regulatory Exclusivity 19 - NON CONFIDENTIAL - Portfolio by program · 6 patent families · 102 issued / 9 pending worldwide Program Patents Claim type Base expiry Follow-on / new filings Reg exclusivity add-on GRI-0621 3 US + 20 foreign issued Medical use 2032 + ODE 3 provisionals (Apr 2026) → non-prov by Apr 2027 → issued claims to ~2047 +7 yr ODE US (granted Jun 2026) · +10 yr ODD EU/JP (in prep) GRI-0803 3 US + 17 foreign issued CoM + medical use 2032 + NCE Racemate, polymorph & formulation filings planned 2026–2028 → issued claims to ~2046–2048 +5 yr NCE from approval · ODD overlay per indication GRI-0729 4 US + 13 foreign issued CoM + medical use 2032 + NCE Back-up chemotype; formulation filings gated to dev decision +5 yr NCE from approval GRI-0124 16 foreign issued · US + 5 pending Medical use 2035 Continuation strategy for PSC + additional autoimmune subsets +ODD overlay (PSC — orphan-eligible) Library 500+ NKT- modulator compounds CoM family Beyond 2032 Each advanced hit is NCE- eligible → fresh 20-yr clock per filing +5 yr NCE per advanced compound Layered exclusivity horizon Base estate 2032 · ODD stack late 2030s · new filings, which, if issued, would provide protection into the late 2040s Issued base estate ODD stack (US +7 / EU +10) from approval date Apr 2026 provisionals → ~2047 GRI-0803 racemate / polymorph / formulation → ~2046–2048 Sequential per-indication ODE LN · SPMS · PSC · RA-ILD · SSc-ILD 2028 2032 2036 2040 2044 2048 Base estate · issued medical-use patents (GRI-0621) 3 US + 20 foreign issued · expire 2032 (absent PTA/PTE) US 10,925,886 (Feb 2021) · US 11,660,309 (May 2023) · US 9,949,996 (2018) · priority 22 June 2012 Validated: AU, BR, CA, CN, EPO (9 EU states), HK, JP, KR, MX, RU 505(b)(2) reliance · Tazoral NDA 21-701 safety db >1,700 pts · ODD granted Jun 2026 · Fast Track + BTD post-Stage 1 Every indication in the Apr 2026 provisionals is independently orphan-eligible IPF US ODD granted Jun 2026; EU/JP planned LN <200K US (FDA Sentinel); EU EU/3/01/064 SPMS ~123K US prevalence; FDA OPD granted PSC US + EU orphan precedent (established) RA-ILD 3.2–6 / 100K (~10–20K US patients) SSc-ILD nintedanib US + EU ODD on record Each ODD carries its own 7-yr US / 10-yr EU clock from its own approval date Apr 2026 provisionals · method-of-use claims that extend enforceable IP into the mid-to-late 2040s 052422-510P01US App # 64/054,338 · Combination therapy · RARβ/γ + antifibrotic Compositions and Methods for Treating Fibrosis Indications named in claims: IPF · SSc-ILD · RA-ILD · PSC · LN. Named partners include nintedanib, pirfenidone, nerandomilast, admilparant, zelasudil, rentosertib, LYT-100, axatilimab, bersiporocin, TDI-01. 052422-511P01US App # 64/054,343 · Method-of-treatment · cough in fibrosis patients Antitussive Compositions and Methods of Use 1–10 mg unit dose oral formulation. Positions in-fibrosis cough label with standalone RCC optionality. Optional combo with antifibrotic, treprostinil, nalbuphine ER, or ACE inhibitor. 052422-512P01US App # 64/054,352 · Method-of-treatment · on-antifibrotic GI toxic ity Compositions and Methods for Treating GI Toxicity Protects tolerability-inversion positioning. Supports on-nintedanib, on- nerandomilast, on-rentosertib combination use. Method-of-use — not a new indication.
Market Opportunity 20 - NON CONFIDENTIAL - Market gap · mechanistic concordance · development timeline · exclusivity runway 1 · The market gap Large market · high discontinuation on approved AFT · big incremental TAM to capture 2035 US branded IPF opportunity $6-9B 6-9% CA GR · US = 75% of branded revenue AFT 12-mo discontinuation (GI tox) ~50% Only ~10% of US IPF patients on approved AFT Incremental TAM · closing 1/3 gap $5-9B Safety profile enables retention and new starts 2 · Multi-modal concordance All five readouts point to the same RARβ/γ-driven mechanism ✓ Transcriptomic (RNA-seq) Immune re-balance · fibrolysis · BM repair · AT2/AT1 · antitussive ✓ Proteomic (Nordic PROC3) Collagen turnover ↓ · fibrolysis ✓ Cellular (spectral flow) Th2 → Th1 · CCR4 ↓ · iNKT TCR ↑ ✓ Physiologic (FVC / HRCT) Lung repair signal ✓ Symptomatic (cough, GI) Antitussive + GI-protective 3 · Adaptive Ph 2b/3 vs. legacy sequential design One pivotal replaces sequential P2b + P3 Legacy (P2b then P3) Ph 2b Ph 3 Adaptive Ph 2b/3 (base) Stage 1 Stage 2 Adaptive · aggressive (Rev. 2) Stage 1 Stage 2 4 · LOE runway Three overlapping layers of protection · runway to late 2040s if pending IP grants Issued base estate Composition & method patents from tazarotene family Orphan Drug Exclusivity 7-yr US market exclusivity from FDA approval (Feb 2033 base) New patent applications (2026, pending) — to ≈2048 if granted SOC combination · antitussive · GI-protection 2026 2030 2035 2040 2045 2050
A New Approach to Inflammatory Diseases NASDAQ: GRI | gribio.com Thank You! Marc Hertz CEO 619-400-1170 mh@gribio.com Investor Relations JTC Team 833-475-8247 gri@jtcir.com
Exhibit 99.2
GRI Bio Presents New Phase 2a Data at ERS 2026 Defining GRI-0621's Mechanism of Action in IPF Across Nine Mechanistic Pillars
New whole blood RNA sequencing data identified coordinated, consistent change in genes governing immune re-balancing, myofibroblast inhibition, fibrolysis, basement membrane repair, re-epithelialization, antitussive effect and GI protection
Signals observed from at least two independent measurement modalities, including RNA sequencing, serum extracellular matrix biomarkers, spectral flow cytometry and clinical readouts, supported each of the nine pre-specified mechanistic pillars, defining a repair phenotype with anti-fibrotic and pro resolving effects
Approximately 2x–2.5x as many GRI-0621-treated patients experienced an FVC increase compared with placebo; placebo-adjusted FVC change from baseline at Week 12 was +99 mL overall and +139 mL on background standard-of-care antifibrotic therapy
Totality of Phase 2a findings supports advancement of GRI-0621 in the IPF program and further evaluation in a longer-duration study
LA JOLLA, CA, September 8, 2026 -- GRI Bio, Inc. (NASDAQ: GRI) ("GRI Bio" or the "Company"), a biotechnology company developing innovative therapies for inflammatory, fibrotic and autoimmune diseases, today announced new translational biomarker data from the Phase 2a GRI-0621-IPF-02 study evaluating GRI-0621 (oral tazarotene) in patients with idiopathic pulmonary fibrosis ("IPF"). The new data, together with the study's lung function and safety results, were presented in a late-breaking oral presentation and three posters at the 2026 European Respiratory Society ("ERS") Congress in Barcelona, Spain.
The data presented at ERS integrate, for the first time, four independent measurement modalities from the same 35-patient study population: whole-blood RNA sequencing, an expanded 12-marker serum extracellular matrix ("ECM") neo-epitope panel, 28-color spectral flow cytometry of paired blood and bronchoalveolar lavage samples, and clinical and patient-reported readouts. Across these modalities, the Phase 2a evidence resolves into nine coherent mechanistic pillars that define how selective RARβ/γ agonism by GRI-0621 acts in IPF: immune re-balancing, reduced lung injury, myofibroblast inhibition, fibrolysis, basement-membrane repair, re-epithelialization, FVC stabilization, antitussive effect and gastrointestinal protection. Each pillar is supported by direction-consistent signals from at least two independent modalities.
Newly reported observations from whole-blood RNA sequencing of 72 curated anchor genes, 28-color spectral flow cytometry of paired blood and bronchoalveolar lavage samples and an expanded 12-marker serum ECM panel provide concordant, direction-consistent signals across the mechanistic pillars. Eighteen anchor transcripts reached statistical significance (FDR<0.05), including ALDH1A2 ↑ confirming pharmacodynamic engagement of the retinoic acid receptor pathway, and 13 flow cytometry readouts reached p<0.05. Key concordant signals included:
•Dismantling of the pro-fibrotic Th2 response: A Th2-to-Th1 shift was observed at both the RNA and protein levels: CCR4 ↓, IL4 ↓ and IL13 ↓ by RNA sequencing, mirrored by flow cytometry showing CCR4 ↓ across six immune lineages, IL-4 ↓, IL-13 ↓ and IFN-γ ↑, together with Th17 inhibition (IL-17A ↓), reduced TGF-β and restored iNKT T-cell receptor expression consistent with iNKT inactivation increased HLA-DR on lung macrophages indicates immune re-programming rather than immune suppression.
•Myofibroblast inhibition through suppression of the TGF-β and ROCK2 pathways: RNA sequencing suggested coordinated downregulation along the TGF-β axis (ADAMTS1 ↓, F2R ↓, TXNDC5 ↓, LTBP1 ↓ and TGFBR2 ↓, with upregulation of the negative-feedback regulators SMAD6/7 ↑ and PMEPA1 ↑, and downstream FN1 ↓, CCN2/CTGF ↓ and TGFB1 ↓) and the ROCK2 contractility axis (RHOA/B ↓ → ROCK2 ↓ and MYL12A ↓ → ACTA2 ↓, LIMK1 ↓, CFL1 ↓, TLN1/VCL ↓ and MRTFA ↓ → SRF ↓), corroborated by reduced TGF-β protein on flow cytometry and reduced serum synthesis of the fibrillar collagens (PRO-C3 ↓, PRO-C6 ↓).
•Fibrolysis: Serum degradation markers of type III and type VI collagen (C3M ↑, CTX-III ↑, C6M ↑) rose while their synthesis markers (PRO-C3 ↓, PRO-C6 ↓) fell, shifting all three synthesis-to-degradation ratios toward net fibrolysis (placebo-adjusted PRO-C3/C3M −13.6, PRO-C3/CTX-III −15.9 and PRO-C6/C6M −14.0 percentage points), concordant with RNA sequencing (ADAMTS1 ↓, MMP1 ↓, PLOD1 ↓, COL1A2 ↓, COL3A1 ↓, COL6A2/A3 ↓).
•Basement-membrane repair: Type IV collagen, the network-forming collagen of the alveolar basement membrane, moved in the opposite direction to the fibrillar collagens. Serum PRO-C4 ↑ (synthesis) and C4Ma3 ↓ (degradation), a placebo-adjusted PRO-C4/C4Ma3 shift of +13.6 percentage points toward net repair, concordant with RNA sequencing upregulation of the basement-membrane genes COL4A1/A2 ↑, LAMA3 ↑ and COL17A1 ↑ and the anti-fibrotic matricellular protein CCN3 ↑.
•AT2/AT1 re-epithelialization: Downstream of basement-membrane repair, RNA sequencing suggested a coordinated alveolar repair program: ALDH1A2 ↑, NAPSA ↑ and SFTPB ↑ (type 2 alveolar epithelial cell identity), NUPR1 ↑, CRB3 ↑, CAV1 ↑ and DLK1 ↑ (AT2-to-AT1 differentiation and restored epithelial polarity), and AGER ↑ and AQP5 ↑ (type 1 alveolar epithelial cell markers), with FVC and dyspnea as functional readouts.
•Antitussive: Treatment-emergent cough was 0% on GRI-0621 versus 25% on placebo, consistent with RNA sequencing evidence of epithelial-barrier restoration (CAV1 ↑, TNFSF10/TRAIL ↓), reduced C-fiber excitability (HTR1B ↓, TAC3 ↓, CALCB ↓) and reduced peripheral sensory transduction (TRPA1 ↓, TRPV1 ↓).
•GI protection: Diarrhea (17% vs. 33%) and weight loss (0% vs. 17%) were less frequent on GRI-0621 than placebo despite higher background nintedanib use in the GRI-0621 arm, consistent with RNA sequencing showing reduced mucosal inflammatory tone and iNKT inhibition (ARG2 ↓, CCR4 ↓, MRC1 ↓) and upregulation of mucosal-repair and vascular-protective growth factors (FGF2 ↑, FGFR1/3 ↑, FLT1 ↑, FLT4 ↑, PDGFA/B/C ↑, VEGFA ↑).
"What is emerging from the Phase 2a dataset is a profile we believe is unique among IPF programs," said Marc Hertz, PhD, Chief Executive Officer of GRI Bio. "Approved antifibrotics slow lung function decline but have not been shown to rebuild lung architecture. With GRI-0621, we observed an anti-fibrotic effect, inhibition of myofibroblasts and a shift toward net breakdown of fibrillar collagen, but we also saw something more: a concordant signal of basement-membrane repair, with a net gain in type IV collagen at both the gene and protein level, followed by activation of the genes that drive type 2 alveolar cells to become the type 1 cells that line a functioning alveolus. Anti-fibrotic activity, basement-membrane repair and re-epithelialization, observed together and in the same patients across four independent modalities, is the signature of a repair phenotype. We believe this is why we see the FVC signal we do after only 12 weeks, and it is what gives us confidence to advance GRI-0621 into a longer-duration study."
The exploratory lung function findings were consistent with the mechanistic data. At Week 12, 39% of GRI-0621-treated patients experienced an FVC increase of ≥30 mL compared with 20% on placebo, rising to 50% among patients receiving background standard-of-care ("SOC") antifibrotic therapy, approximately 2x–2.5x the placebo responder rate. At the other end of the distribution, only 8% of GRI-0621-treated patients experienced an FVC decline of ≥10% compared with 20% on placebo, a 60% relative reduction in the accelerated-decline event rate. Placebo-adjusted FVC change from baseline at Week 12 was +99 mL overall and +139 mL on background SOC. Because spirometry is subject to visit-to-visit variability and outliers in a small study, a family of ten post hoc robustness sensitivity analyses were performed. Every analysis remained directionally positive, with estimates converging on +40 to +65 mL overall and +67 to +89 mL in the background SOC subset. FVC was an exploratory endpoint and the study was not powered for statistical significance.
GRI-0621 was well tolerated over 12 weeks. There were no serious treatment-emergent adverse events in the GRI-0621 arm (0% vs. 8% on placebo) and no drug-related serious adverse events. Adverse events were consistent with the known retinoid class profile (dry lips, dry skin, arthralgia and myalgia), all Grade 1–2 and managed with routine supportive care. GRI-0621-treated patients reported less treatment-emergent cough (0% vs. 25%), dyspnea (4% vs. 17%) and diarrhea (17% vs. 33%) than placebo, despite higher background nintedanib use in the GRI-0621 arm. No clinically meaningful changes in liver enzymes, triglycerides or LDL cholesterol were observed and no night vision, hearing or neuropsychiatric events were reported.
Key Findings from the Phase 2a GRI-0621-IPF-02 Study
•Nine mechanistic pillars defined: Direction-consistent signals from at least two of four independent measurement modalities supported each of the nine pre-specified mechanistic pillars: immune re-balancing, reduced lung injury, myofibroblast inhibition, fibrolysis, basement-membrane repair, re-epithelialization, FVC stabilization, antitussive effect and GI protection.
•Strong concordance across biomarker modalities: RNA sequencing (18 of 72 anchor transcripts at FDR<0.05), spectral flow cytometry (13 readouts at p<0.05) and serum ECM biomarkers were direction-consistent in the same patients, showing dismantling of the Th2 response, suppression of the TGF-β and ROCK2 pathways, net fibrolysis of type III and VI collagen, net repair of type IV collagen basement membrane and an AT2-to-AT1 re-epithelialization program, alongside antitussive and GI-protective signals.
•Favorable FVC responder and decline rates: 39% of GRI-0621-treated patients experienced an FVC increase of ≥30 mL compared with 20% on placebo, increasing to 50% among patients receiving background SOC therapy. Only 8% of GRI-0621-treated patients experienced an FVC decline of ≥10% compared with 20% on placebo, a 60% relative reduction.
•Positive effect on FVC: Placebo-adjusted FVC change from baseline at Week 12 was +99 mL overall and +139 mL among patients receiving background SOC antifibrotic therapy.
•Robust FVC sensitivity analyses: All ten post hoc robustness sensitivity analyses of the FVC endpoint remained directionally positive, with estimates converging on +40 to +65 mL overall and +67 to +89 mL on background SOC. FVC was an exploratory endpoint and the study was not powered for statistical significance.
•Favorable tolerability: GRI-0621 was well tolerated over 12 weeks, with no serious treatment-emergent adverse events compared with 8% on placebo, zero drug-related serious adverse events, less cough (0% vs. 25%), dyspnea (4% vs. 17%) and diarrhea (17% vs. 33%) than placebo and no hepatic, lipid, visual, auditory or neuropsychiatric safety signals.
Presentation and Posters
•Late-Breaking Oral
Safety, translational biomarkers and lung function with the oral RARβ/γ-selective agonist GRI-0621 in idiopathic pulmonary fibrosis: a Phase 2a randomised, double-blind, placebo controlled trial (GRI-0621-IPF-02)
•Translational Biomarkers
GRI-0621 Phase 2a biomarker study in patients with IPF using gene expression, immune cell activity and collagen markers supports a repair phenotype with strong anti-fibrotic and pro-resolving effects
•Lung Function
GRI-0621 phase 2a biomarker study in patients with IPF: GRI-0621 has a positive effect on FVC after 12 weeks of treatment
•Safety
GRI-0621 phase 2a biomarker study in patients with IPF: a safety signal demonstrating favorable tolerability
GRI-0621-IPF-02 (NCT06331624) was a randomized, double-blind, placebo-controlled Phase 2a study evaluating the safety, translational biomarkers and exploratory lung function of GRI-0621, the Company's oral retinoic acid receptor ("RAR") β/γ-selective agonist. Thirty-five patients with IPF were randomized 2:1 to receive GRI-0621 4.5 mg once daily (n=23) or placebo (n=12) for 12 weeks, with 80% receiving background pirfenidone or nintedanib. Safety was the pre-specified primary endpoint.
Taken together, the Phase 2a data define a mechanism of action for GRI-0621 in IPF that couples immune re-balancing to matrix catabolism and alveolar epithelial repair, supported by direction-consistent signals across four independent modalities, together with a positive effect on FVC after 12 weeks of treatment and favorable tolerability. The Company believes the findings support advancement of GRI-0621 in the IPF program and evaluation in a 52-week study, including concomitant with background pirfenidone or nintedanib.
About GRI Bio, Inc.
GRI Bio is a clinical-stage biopharmaceutical company focused on developing innovative therapies for inflammatory, fibrotic and autoimmune diseases. The Company's lead program, GRI-0621, is an oral RARβ/γ-selective agonist being developed for the treatment of idiopathic pulmonary fibrosis (IPF), a progressive and life-threatening fibrotic lung disease with significant unmet need. GRI-0621 is designed to modulate pathways associated with inflammation, fibrosis and tissue repair and is being evaluated as a potential novel oral therapeutic for patients with IPF.
In addition to GRI-0621, the Company is also developing a pipeline of novel type 2 diverse NKT ("dNKT") agonists for the treatment of systemic lupus erythematosus. Additionally, with a library of over 500 proprietary compounds, GRI Bio has the ability to fuel a growing pipeline.
Forward-Looking Statements
This press release contains "forward-looking statements" within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words such as "anticipate," "believe," "contemplate," "could," "estimate," "expect," "intend," "seek," "may," "might," "plan," "potential," "predict," "project," "target," "aim," "should," "will," "would," or the negative of these words or other similar expressions. These forward-looking statements are based on the Company's current beliefs and expectations. Forward-looking statements include, but are not limited to, statements regarding: the Company's expectations with respect to development and commercialization of the Company's product candidates, the timing of initiation or completion of clinical trials and availability of resulting data, the potential benefits and impact of the Company's clinical trials and product candidates and any implication that the data or results observed in preclinical trials or earlier studies, topline or interim data or trials will be indicative of results of later studies or clinical trials or final data, the Company's beliefs and expectations regarding potential shareholder value and future financial performance, the Company's beliefs about the timing and outcome of regulatory approvals and potential regulatory approval pathways, the Company's expected future milestones, shareholder value and the length of time the Company's current resources will fund its planned operations (which current estimate assumes only initial preparatory activities for GRI-0621 as substantial additional capital or resources will be required to fund a Phase 2b clinical trial of GRI-0621). Actual results may differ from the forward-looking statements expressed by the Company in this press release and consequently, you should not rely on these forward-looking statements as predictions of future events. These forward-looking statements are subject to inherent uncertainties, risks and assumptions that are difficult to predict, including, without limitation risks related to: (1) the Company's inability to maintain the listing of the Company's common stock on The Nasdaq Capital Market and to comply with applicable listing requirements; (2) changes in applicable laws or regulations; (3) the inability of the Company to raise financing in the future; (4) the success, cost and timing of the Company's product development activities; (5) the inability of the Company to obtain and maintain regulatory clearance or approval for its respective products, and any related restrictions and limitations of any cleared or approved product; (6) the inability of the Company to identify, in-license or acquire additional technology; (7) the inability of the Company to compete with other companies currently marketing or engaged in the development of products and services that the Company is currently developing; (8) the accuracy of the estimated size and growth potential of the markets for the Company's products and services, and its ability to serve those markets, either alone or in partnership with others; (9) that later data or clinical trials may be inconsistent with or contrary to data and observations to date, including that later data may not indicate a patient benefit, modulate toxicities or validate a mechanism of action; (10) inaccuracy in the Company's estimates regarding expenses, future revenue, capital requirements and needs for and the ability to obtain additional financing; (11) the Company's ability to protect and enforce its intellectual property portfolio, including any newly issued patents and its ability to obtain any expected patent term extensions, adjustments, exclusivities or disclaimers; and (12) other risks and uncertainties indicated from time to time in the Company's filings with the U.S. Securities and Exchange Commission (the "SEC"), including the risks and uncertainties described in the "Risk Factors" section of the Company's most recent Annual Report on Form 10-K filed with the SEC on January 30, 2026 and subsequently filed reports. Forward-looking statements
contained in this announcement are made as of this date, and the Company undertakes no duty to update such information except as required under applicable law.
Investor Contact:
JTC Team, LLC
Jenene Thomas
(908) 824-0775
GRI@jtcir.com