On April 2, 2026 GENFIT (Euronext: GNFT), a late-stage biopharmaceutical company dedicated to improving the lives of patients with rare and life-threatening liver diseases, reported annual financial results for the year ended December 31, 2025 and provided a corporate update. A summary of the consolidated financial statements is included below.

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Pascal Prigent, CEO of GENFIT commented: "Iqirvo’s performance in its first full year of sales, together with encouraging early results from both our oncology and ACLF assets, were very promising signs for GENFIT last year. 2026 could be even better and significantly accelerate the Company’s trajectory. Indeed, we expect to see continued strong performance from Iqirvo in PBC, while also anticipating a significant acceleration in our diagnostic business. On top of these growing businesses, there are also promising programs further down the pipeline. This summer, we expect to receive full results from our Phase 1b oncology trial, which could become a game changer. In 2027, we anticipate results from the Phase 2 proof‑of‑concept study evaluating NTZ in ACLF that we will start later this year. Looking further ahead, Ipsen’s ongoing development efforts in PSC also have the potential to represent a step change for the Company."

In 2025, GENFIT benefited from the strong commercial performance of Iqirvo1 in Primary Biliary Cholangitis (PBC), driven by Ipsen’s commercial execution. Performance will continue to be closely monitored, and current indicators suggest that Ipsen is on track to deliver results meaningfully above initial expectations. Beyond this existing business, several additional programs in our pipeline or with partners have the potential to generate additional significant value in the future on a scale comparable to, or exceeding, PBC royalties:

In metabolic dysfunction‑associated steatohepatitis (MASH), GENFIT’s diagnostic technology targets a very large and rapidly expanding market, supported by accelerating therapeutic development and deepening engagement from major industry players. In this context, our non-invasive technology is recognized as a critical component of this evolving ecosystem. We believe that the potential royalties deriving from our technology could be very significant. Key catalysts will be reimbursement status and industry partnerships, with multiple initiatives currently underway to drive broader deployment.
In oncology, new Phase 1b clinical data from the GNS561 combination in cholangiocarcinoma (CCA) are expected mid‑year and should provide important insights to inform further development and support progression toward Phase 2.
In Acute-on-Chronic Liver Failure (ACLF), a Phase 2 study evaluating NTZ is expected to start in the second half of this year, marking a significant step forward in this indication.
Finally, in PSC, a market comparable in size to PBC, Ipsen has initiated a Phase 3 study called ELASCOPE2 in February 2026, and currently is the sole company at this stage of development in PSC.
I. 2025 Highlights – including post-closing events

Commercial & partnership highlights

In 2025, GENFIT’s partners achieved significant progress, driving a number of important developments across key programs:

Ipsen’s Iqirvo (elafibranor) in PBC and PSC

PBC: Iqirvo’s net sales for the fourth quarter 2025 amounted to US$88 million, bringing full-year 2025 sales to US$208 million3, triggering the first US$20M commercial milestone payment to GENFIT one year ahead of schedule. This momentum also allowed GENFIT to activate, in January 2026, an additional €30 million tranche under GENFIT’s royalty‑financing agreement with HCRx, enhancing financial flexibility without shareholder dilution.
PSC: Ipsen initiated the first and only global Phase 3 clinical trial, addressing a significant unmet medical need, as no approved therapies currently exist for this severe and progressive disease. PSC represents a substantial untapped market opportunity, comparable in size to second line PBC. Should Iqirvo ultimately receive regulatory approval for this indication, GENFIT would be eligible for additional milestone payments as well as additional double‑digit royalties.
Following the mutual termination of GENFIT’s agreement with Terns in December 2025, Ipsen exercised its contractual opt‑in right to include Greater China in the existing Licensing Agreement, resulting in a worldwide elafibranor license for Ipsen under the same favorable financial terms.

Non-invasive diagnostic technology in MASH

The MASH therapeutics market accelerated in 2025, with near‑blockbuster performance (~US$1 billion in sales) achieved by the first approved therapy in its first year of commercialization, increasing the need for large‑scale, non‑invasive diagnostic, further reinforced by the entry of an additional major therapeutic player in August. Against this backdrop, pricing for NASHnext—developed by Labcorp as a Laboratory Development Test (LDT) under license from GENFIT and based on GENFIT’s proprietary non‑invasive diagnostic technology for identifying at‑risk patients in MASH (formerly NASH)—, was established by U.S. Medicare and Medicaid at the end of 2025. This represents an important step toward reimbursement.

R&D highlights

In 2025, GENFIT advanced its lead clinical programs in ACLF and CCA, reprioritized VS‑01, and continued to assess the potential of multiple mechanisms of action across its research portfolio.

Clinical developments

G1090N/NTZ (ACLF): Our lead program generated preliminary Phase 1 data showing a favorable safety profile and a robust anti-inflammatory activity evidenced through functional ex vivo assays on blood samples from study participants and from cirrhotic donors.
GNS561 (CCA): Encouraging preliminary data were generated from the ongoing Phase 1b study evaluating investigational drug GNS561 with a MEK inhibitor (MEKi) in KRAS mutated CCA, positioning this novel combination as a potential new therapeutic approach for difficult-to-treat cancers.
VS-01 (ACLF): GENFIT decided to discontinue this program in ACLF, following the emergence of a safety signal, prompting a precautionary reassessment of the benefit/risk ratio in this indication, and refocused development in Urea Cycle Disorder (UCD) where the disease biology, patient population and development framework materially differ.

Research developments

SRT–015 (ACLF): Although activity on the ASK1 target has been demonstrated in preclinical models, the in vivo data available to date do not confirm a sufficient benefit, and uncertainties remain regarding the expected effects in ACLF.
CLM–022 (ACLF): Alongside preclinical studies, GENFIT pursued the activities preliminary to clinical development, including pharmacokinetic and nonclinical safety characterization. While the NLRP3 target remains valid, developability challenges with CLM-022 have been identified and will be further assessed.
VS-02-HE (ACLF continuum): VS‑02‑HE is being optimized as an oral formulation designed to act at the colonic level, where ammonia is primarily produced, to minimize its systemic concentration while reducing glutamine levels in the brain. In the first quarter of 2026, regulatory toxicology studies were initiated.
EViv (ACLF): At the end of 2025, GENFIT initiated a research collaboration with EverZom aimed at evaluating the therapeutic potential of extracellular vesicles derived from human adipose‑derived mesenchymal stem cells (hAD‑MSC‑EVs) in Acute Decompensation (AD) and ACLF.
VS-01-HAC (UCD): VS01 was reprioritized to Urea Cycle Disorders (UCD) following the discontinuation of the ACLF program. Positive initial data from a pivotal juvenile toxicology study in Göttingen minipigs supported the tolerability of the compound. VS-01-HAC was granted Rare Pediatric Disease Designation by the FDA for UCD, potentially enabling eligibility for a Priority Review Voucher upon New Drug Application approval.

Other developments

In 2025, GENFIT contributed to positioning ACLF as a strategic focus within the Forum for Collaborative Research, an independent multi‑stakeholder initiative bringing together regulators, industry leaders, academics, clinicians, scientists and patient groups to help shape and accelerate drug development in areas of high unmet medical need.

Financial highlights

The Royalty Financing agreement signed in March 20254 has significantly extended GENFIT’s cash runway, beyond the end of 2028, enabling the Company to further develop its pipeline focused on ACLF and support general corporate purposes. See III. Financial results for further details.

Genfit recorded a revenue of €65.4 million in 2025. This consists of greater than expected royalty revenue of €21.8 million and two milestones totalling €43.6 million, both of which stem from positive market performance of Ipsen’s Iqirvo.

For the year ended December 31, 2025, the Company’s net loss amounted to €86.0 million compared with a net gain of €1.5 million for the year ended December 31, 2024.
Excluding certain one‑time non‑cash operating expenses of €49.1 million, and excluding an estimated €13.3 million in financial expenses arising from faster than expected repayment of the royalty financing, the 2025 net loss would be reduced to €23.6 million. These items are described in more detail below in section III. Financial Results.

Sustainability highlights

B Corp certification was granted at the end of 2025, providing an independent, internationally recognized mark of credibility. This certification underscores GENFIT’s engagement in social, societal, environmental and governance matters as the Company continues to execute its ESG roadmap on schedule.

Corporate governance updates

Mr. Tristan IMBERT was appointed as a director for a three-year term by the General Meeting of Shareholders held on June 17, 2025 and joined the Audit Committee and ESG Committee following his appointment. The terms of office of Mr. Eric BACLET and Ms. Katherine KALIN as directors were renewed for a period of three years. Mr. John BROZEK replaced Ms. Florence SÉJOURNÉ as permanent representative of Biotech Avenir SAS on the Company’s Board of Directors. Dr. Pejvack MOTLAGH replaced Dr. Carol ADDY as Chief Medical Officer and member of the Executive Committee in November 2025, following her retirement on June 30, 2025. Sakina SAYAH-JEANNE, formerly Executive Vice President of Research and Translational Science and member of the Executive Committee, replaced Dean HUM, Chief Scientific Officer following his retirement on September 30, 2025.

II. 2026 Outlook

Commercial and partnership outlook

Ipsen’s Iqirvo (elafibranor) in PBC and PSC

Ipsen is expected to publish its first‑quarter 2026 financial results on April 23, 2026. For further information on the development of Iqirvo in PBC and PSC, please refer to Ipsen’s news flow and financial calendar: View Source

Non-invasive diagnostic technology in MASH

Building on the therapeutic market momentum observed in 2025, and the expected evolution of the competitive landscape with the entry of additional large pharmaceutical players, the MASH diagnostics market is expected to further develop in 2026. Addressing this opportunity at scale will require reliable and scalable solutions to support patient identification, treatment decision‑making and longitudinal monitoring across care pathways. In this context, GENFIT’s technology is already referenced in international clinical guidance as the only fully blood‑based approach for identifying at‑risk MASH patients, recognized by the LITMUS and NIMBLE consortia and supported by a robust body of scientific literature. Looking ahead, further progress in 2026 will depend on a combination of factors, including reimbursement and payer adoption, demand generated through broad pharmaceutical programs, and advances toward an IVD‑labeled version to support wider clinical use.

R&D outlook

Clinical outlook

G1090N/NTZ (ACLF): GENFIT will engage with regulatory authorities, including the U.S. Food and Drug Administration (FDA), to determine the best approach for progressing to a Phase 2 proof-of-concept in inflammatory conditions such as ACLF where systemic immune dysregulation is a critical driver of disease progression. Initiation remains targeted for the second half of 2026, with data expected in 2027. In March 2026, Orphan Drug Designation (ODD) was granted for NTZ for the treatment of ACLF.
GNS561 (CCA): Phase 1b dose escalation is progressing as planned, with additional cohort data expected in mid‑2026. The Phase 1 study is designed to assess safety, define the recommended Phase 2 doses for the combination, and evaluate preliminary signs of activity. Initiation of Phase 2 remains targeted for the second half of 2026. In parallel, GENFIT will investigate the biological rationale for autophagy inhibition in the emergence of resistance to standards of care. These studies will aim to assess the therapeutic potential of new combination strategies, associating GNS561 with other agents.
Research outlook

SRT-015 (ACLF): Current work focuses on finishing the preclinical activities to decide by the end of the first semester of 2026 if we move the program into a first‑in‑human clinical trial.
CLM-022 (ACLF): Ongoing work aims to strengthen the translational rationale for NLRP3 inhibition in the indications of AD and ACLF.
VS-02-HE (ACLF continuum): Pharmacological studies are ongoing, and the regulatory toxicology studies are expected to be completed by early 2027. Subject to confirmation, a first‑in‑human trial could be launched in the second half of 2027.
EViv (ACLF): GENFIT and EVerZom plan to conduct exploratory studies to evaluate the efficacy of EViv in ACLF, with a decision point targeted mid-2027 on whether to advance into clinical development.
VS-01-HAC (UCD): A plan of action is currently executed, aimed at securing the developability of VS‑01 in UCD, before potentially initiating a first clinical trial.

Other developments

In May 2026, ahead of its annual congress, the European Association for the Study of the Liver (EASL) will bring together leading international learned societies, spanning North America, Asia‑Pacific, Latin America and Africa, represented by AASLD5, APASL6, ALEH7 and SOLDA8, to jointly address ACLF. This pre‑congress program sends a strong signal for patients, healthcare providers and industrial stakeholders, underscoring growing alignment and momentum across the global hepatology community.

(Press release, Genfit, APR 2, 2026, https://ir.genfit.com/news-releases/news-release-details/genfit-reports-full-year-2025-financial-results-and-provides [SID1234664148])

On April 2, 2026 Biodexa Pharmaceuticals PLC (Nasdaq: BDRX) ("Biodexa" or "Company"), a clinical stage biopharmaceutical company developing a clinical stage biopharmaceutical company developing innovative products focused on the treatment or prevention of gastrointestinal cancers, reported that it has partnered with Syngene International Ltd (BSE: 539268, NSE: SYNGENE) ("Syngene") for the manufacture of both MTX240 active pharmaceutical ingredient and dosage form.

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Commenting, Dan Palmer, Vice President, Technology at Biodexa said "We are delighted to be partnering with Syngene for the second time. Syngene manufactured tolimidone dosage form for us on time and on budget and, given the license for MTX240 from Otsuka was only signed in early February, they have once again demonstrated their responsiveness and flexibility in designing a program to manufacture GMP product within only a few weeks"

About MTX240, its Unique Mechanism of Action, Clinical Rationale and Next Steps
Molecular glue technology represents a novel approach that induces targeted protein interactions, offering a distinct mechanism of action to conventional kinase inhibitors for rare oncology indications.

Gastrointestinal Stromal Tumors ("GIST") is mostly driven by activating mutations in the KIT and/or PDGFR receptor tyrosine kinase. While tyrosine kinase inhibitors (TKIs) such as imatinib, sunitinib, and regorafenib are reported to have significantly improved outcomes for GIST patients, resistance almost always develops through secondary KIT or PDGFR mutations or activation of alternative signalling pathways. This represents a substantial clinical challenge with limited therapeutic options for patients once they have cycled through the available TKIs.

MTX240 acts as a molecular glue, bringing two intracellular proteins, PDE3a and SLFN12, specifically co-expressed by GIST cancer cells, into close proximity to form a stable complex. This interaction stabilizes SLFN12, enabling it to drive RNase-mediated apoptosis in GIST cells through a mechanism independent of KIT signalling. By triggering cell death through this alternative pathway, MTX240 is designed to overcome the resistance mechanisms that render TKI-resistant GISTs refractory to conventional kinase inhibitors. This novel mechanism may provide clinical benefit for a significant proportion of GIST patients, not only those who have developed resistance to TKIs.

Biodexa is planning to file an IND and initiate a Phase 1b/2a study towards the end of the year. The study will likely be in two parts: a dose escalation part to establish a safe and tolerable dose followed by an expansion part designed to generate an efficacy signal in TKI-resistant GIST patients.

(Press release, Biodexa Pharmaceuticals, APR 2, 2026, View Source [SID1234664164])

On April 2, 2026 INOVIO Pharmaceuticals, Inc. (Nasdaq: INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, reported the pricing of an underwritten public offering of 12,500,000 shares of its common stock and accompanying Series A warrants to purchase up to 12,500,000 shares of its common stock (or pre-funded warrants in lieu thereof) at an exercise price of $1.40 per share of common stock and Series B warrants to purchase up to 12,500,000 shares of its common stock (or pre-funded warrants in lieu thereof) at an exercise price of $1.40 per share of common stock, at a combined public offering price of $1.40 per share of common stock and accompanying Series A and Series B warrants. All of the securities in the offering are being sold by INOVIO. The offering is expected to close on or about April 6, 2026, subject to the satisfaction of customary closing conditions. INOVIO also granted the underwriter an option for a period of 30 days to purchase up to 1,875,000 additional shares of the Company’s common stock and Series A warrants to purchase up to 1,875,000 additional shares of its common stock and Series B warrants to purchase up to 1,875,000 additional shares of its common stock at the public offering price, less the underwriting discounts and commissions.

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The gross proceeds from the offering, before deducting the underwriting discounts and commissions and offering expenses payable by INOVIO, excluding any exercise of the underwriter’s option to purchase additional securities and assuming no exercise of the accompanying Series A and Series B warrants, are expected to be approximately $17.5 million.

Piper Sandler is acting as sole manager for the offering.

A shelf registration statement relating to the shares of common stock and accompanying Series A and Series B warrants offered in the offering described above was filed with the Securities and Exchange Commission ("SEC") on November 9, 2023 and declared effective by the SEC on January 31, 2024. The offering is being made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. A preliminary prospectus supplement and accompanying prospectus relating to and describing the terms of the offering were filed with the SEC and are available on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus, when available, may also be obtained by contacting: Piper Sandler & Co., 350 North 5th Street, Suite 1000, Minneapolis, Minnesota 55401, Attention: Prospectus Department, by telephone at (800) 747-3924, or by e-mail at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy the securities being offered, nor shall there be any sale of the securities being offered in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

(Press release, Inovio, APR 2, 2026, View Source [SID1234664149])

On April 2, 2026 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, reported a clinical collaboration with Incyte (Nasdaq:INCY), to evaluate the combination of muzastotug (ADG126) and INCA33890, a TGFβR2 × PD-1 bispecific antibody, in patients with microsatellite stable colorectal cancer (MSS CRC) with or without liver metastases.

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Muzastotug in combination with Merck’s (known as MSD outside of the United States and Canada) anti-PD-1 therapy, KEYTRUDA (pembrolizumab) has demonstrated encouraging overall response rates and durable responses in a Phase 1b/2 trial in 3L MSS CRC patients. As a monotherapy, INCA33890 has demonstrated promising clinical efficacy and safety in immune checkpoint sensitive and insensitive cancers, including MSS CRC with and without liver metastases. Incyte has recently initiated a Phase 3 study (NCT07284849) evaluating bevacizumab and FOLFOX (standard of care chemotherapy) with or without INCA33890 in 700 first-line MSS CRC patients.

"This strategic collaboration marks the second instance in which Adagene’s SAFEbody technology is being paired with a leading PD-1–based bispecific, further reinforcing muzastotug’s potential as a backbone immunotherapy with a wider therapeutic index for next-generation immuno-oncology combinations," said Peter Luo, Ph.D., CEO and President of R&D at Adagene. "We look forward to the clinical insights this study may provide to support our belief that muzastotug has the potential to both improve overall response rate and extend survival, meaningfully enhancing the clinical benefit for patients."

"This collaboration allows us to explore a novel combination approach for patients with microsatellite stable colorectal cancer, a disease that remains resistant to current immunotherapies," said Pablo J. Cagnoni, M.D., President, Head of Research & Development at Incyte. "By evaluating INCA33890 in combination with muzastotug, we aim to better understand whether complementary mechanisms may help enhance anti-tumor immune responses particularly for patients with liver metastases, who have an especially poor prognosis and limited treatment options."

Muzastotug, a masked anti-CTLA-4 SAFEbody with FDA Fast Track designation, is currently being evaluated in multiple ongoing studies, including:

A Phase 1b/2 clinical trial in combination with pembrolizumab in MSS CRC patients without liver metastases.
A randomized Phase 2 study in MSS CRC patients without liver metastases designed to determine the optimal dose to advance into a Phase 3 registration trial.
A Phase 1b/2 dose escalation and expansion study of muzastotug in combination with Sanofi’s SAR445877 (PD-1 x IL-15 fusion protein) in adults with advanced solid tumors.
Under terms of the agreement, Incyte will sponsor and conduct the study and Adagene will provide clinical trial supply of muzastotug. The planned dose escalation portion of the study will evaluate safety and tolerability, followed by an efficacy expansion cohort in patients with chemotherapy-refractory MSS CRC patients with and without liver metastases. MSS CRC is well-known to be largely non-responsive to anti-PD-1 / PD-L1 therapy. INCA33890 monotherapy has demonstrated promising initial clinical efficacy and safety in immune checkpoint sensitive/insensitive tumors, including MSS CRC with and without liver metastases.

(Press release, Adagene, APR 2, 2026, View Source [SID1234664165])

On April 2, 2026 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, reported results from the latest data cut from its Phase 1b/2 study of muzastotug in patients with advanced microsatellite stable colorectal cancer (MSS CRC) with no liver metastases. FDA has designated muzastotug in combination with Merck’s (known as MSD outside of the United States and Canada) anti-PD-1 therapy, KEYTRUDA (pembrolizumab), as a Fast Track product for adult patients with microsatellite stable metastatic colorectal cancer (MSS mCRC) without current or active liver metastases.

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"Historically, patients with late-line MSS colorectal cancer have faced limited options and poor outcomes with standard immunotherapies," stated Dr. Marwan Fakih, Professor of Medical Oncology and Therapeutics Research at City of Hope. "The latest data on muzastotug combined with pembrolizumab shows a meaningful clinical benefit for this heavily pretreated group. Beyond the encouraging response durations and overall survival rates—particularly at the 20 mg/kg dose—the safety results are a key differentiator. It potentially allows patients to sustain treatment longer, paving the way for durable disease control while mitigating the severe treatment-related toxicities that have long limited anti-CTLA-4 treatments."

"These data offer strong clinical support for our masked antibody platform, demonstrating our potential to expand the therapeutic window for CTLA-4 therapy," said Peter Luo, Ph.D., CEO and President of R&D at Adagene. "The clear dose-dependent response observed at 20 versus 10 mg/kg, along with early survival indicators that track consistently with the immunotherapy-like long tail—highlighted by a 48% survival rate at two years in our mature 10 mg/kg cohorts —gives us high confidence in this program’s potentially differentiated profile. Supported by our FDA Fast Track designation, we remain focused on executing our randomized Phase 2 trial and collaborating with regulatory authorities to finalize an optimal dose and registration path."

Updated Interim Efficacy Results from Phase 1b/2 Trial
Previous results from a data cut on April 22, 2025 were presented at ASCO (Free ASCO Whitepaper) in June 2025. As of the latest data cut on January 24, 2026, a total of 67 MSS CRC patients with no liver metastases, including those with peritoneal involvement, have been treated with muzastotug at a dose of either 10 mg/kg or 20 mg/kg, in combination with pembrolizumab. The 10 mg/kg dose was administered once every three weeks or once every six weeks. The 20 mg/kg dose was administered once as a loading dose, followed by 10 mg/kg every three weeks, or 20 mg/kg every six weeks.

Among 65 efficacy-evaluable patients in the dose expansion phase, those in the combined 10 mg/kg cohorts (N=39) demonstrated an ORR of 13% (5/39), which was comprised of an ORR of 0% (0/10) in the Q6W regimen cohort and an ORR of 17% (5/29) in the Q3W cohort. The higher response rates in the Q3W cohort and robust safety, to keep patients stable without new lesions, in the Q6W cohort helped inform the decision for the dosing regimens utilized in Arm A of the ongoing randomized Phase 2 trial.

The combined 20 mg/kg cohorts (N=26) demonstrated a confirmed ORR of 31% (8/26), including 25% (3/12) in the Q6W cohort and 36% (5/14) in the 20 mg/kg loading dose cohort (20 mg/kg, followed by 10 mg/kg Q3W). The higher response rate in the 20 mg/kg cohorts helped inform the 20 mg/kg induction/maintenance dosing regimen utilized in Arm B of the ongoing randomized Phase 2 trial.

Median progression-free survival was 4.8 months in the 10 mg/kg cohorts and 6.7 months in the 20 mg/kg cohorts. Notably, median PFS was 15.4 months among the 14 patients in the 20 mg/kg loading dose cohort, compared with 4.9 months among the 12 patients in the 20 mg/kg Q6W cohort, further supporting the induction/maintenance approach now being evaluated in the ongoing randomized Phase 2 study.

Muzastotug
+ Pembrolizumab 200 mg Q3W 10 mg/kg 20 mg/kg
Subpopulation (N) Combined
(N=39) Q6W
(N=10) Q3W
(N=29) Combined
(N=26) Q6W
(N=12) 20 mg/kg x1
+ 10 mg/kg Q3W
(N=14)
ORR, % (95% CI) 13
(4-27) 0a
(0-31) 17
(6-36) 31
(14-52) 25
(5-57) 36
(13-65)
BoR, N (%)
CR 0 0 0 1 (4) 1 (8) 0
PR 5 (13) 0 5b (17) 7 (27) 2 (17) 5 (36)
SD 24 (62) 7 (70) 17 (59) 14 (54) 7 (58) 7 (50)
DCR (CR+PR+SD), %, (95% CI) 74
(58-87) 70
(35-93) 76
(56-90) 85
(65-96) 83
(52-98) 86
(57-98)
Median PFS, months (95%CI) 4.8
(2.6-6.7) 4.5
(1.4-7.1) 4.8
(2.6-6.7) 6.7
(2.7-NA) 4.9
(1.2-NA) 15.4
(2.6-NA)
6-month PFS, %, (95% CI) 39.6
(24.3-54.6) 40
(12.3-67) 39.6
(21.9-56.8) 50.4
(29.5-68.1) 45.5
(16.7-70.7) 54.5
(25.4-76.5)
Efficacy evaluable set (participants who received ≥1 post-baseline scheduled imaging scan)
a. One patient with target lesion assessed as "PR", overall assessment as "PD" due to new lesion.
b. Including one unconfirmed PR (10 mg/kg Q3W)

Median overall survival (OS) for the 10 mg/kg cohorts was 19.8 months with a 23.8-month median follow-up. Median OS for the 20 mg/kg cohorts was not yet reached, with a median follow-up of 13.1 months. Patients in the 20 mg/kg cohorts demonstrated a 1-year OS rate of 80.8%, while patients in the 10 mg/kg cohorts demonstrated an OS rate of 70.1% at 12 months and 48% at 24 months.

Updated Interim Safety Results from Phase 1b/2 Trial
As of the January 24, 2026 data cutoff, across 67 patients in all cohorts, there was a low 4% overall discontinuation rate, no dose limiting toxicities, and no treatment-related Grade 4 or 5 adverse events (TRAEs). Grade 3 TRAEs were 15% in the combined 10 mg/kg cohorts (0% Q6W; 20% Q3W) and 38% in the combined 20 mg/kg cohorts (25% Q6W; 50% loading dose cohort), which were generally transient and manageable.

The most common treatment-related adverse events were pruritus, fatigue, hypothyroidism, and diarrhea. Regarding GI-related adverse events, the overall incidence of diarrhea, colitis and immune-mediated enterocolitis was relatively low, and such events were generally transient and manageable. The three patients with Grade 3 colitis had all recovered at the time of data cut-off. Infliximab use was low, with approximately 10% of patients requiring its use for management of GI toxicity.

Preferred Term All Grade
n (%) Grade 1
n (%) Grade 2
n (%) Grade 3
n (%)
Any TRAE 57 (85.1) 15 (22.4) 26 (38.8) 16 (23.9)
Pruritus 25 (37.3) 20 (29.9) 5 (7.5) 0
Fatigue 15 (22.4) 12 (17.9) 3 (4.5) 0
Hypothyroidism 13 (19.4) 3 (4.5) 10 (14.9) 0
Diarrhea 12 (17.9) 5 (7.5) 4 (6) 3 (4.5)
Adrenal insufficiency 10 (14.9) 1 (1.5) 9 (13.4) 0
Decreased appetite 8 (11.9) 6 (9) 2 (3) 0
Alanine aminotransferase increased 7 (10.4) 2 (3) 4 (6) 1 (1.5)
Arthralgia 7 (10.4) 5 (7.5) 2 (3) 0
Nausea 7 (10.4) 4 (6) 3 (4.5) 0
Colitis 7 (10.4) 0 4 (6) 3 (4.5)
Immune-mediated enterocolitis 3 (4.5) 0 2 (3) 1 (1.5)

Ongoing Phase 2 Randomized Trial
The randomized Phase 2 trial design, incorporated into the Company’s existing protocol for the Phase 1b/2 Trial (NCT05405595) was established following a meeting with the US Food and Drug Administration (FDA) in 2025 and is evaluating two different dose regimens. The first patient was treated in October 2025, and results are expected in 1H 2027. The Company intends to take full advantage of the recent Fast Track designation by the FDA to initiate a potential registration study of muzastotug pending further FDA feedback regarding the dose regimen identified from ongoing trials.

Patient Population: The trial will enroll up to 60 late-line patients with MSS CRC without liver metastases, including those with peritoneal metastasis/involvement. Patients are randomized 1:1 into one of two treatment arms with muzastotug in combination with pembrolizumab.

Dose and Regimen: Both arms utilize an induction/maintenance regimen, without cycle limitations for muzastotug.

Arm A: 10 mg/kg induction dose of muzastotug plus 200 mg pembrolizumab every 3 weeks (Q3W) for 4 doses followed by one 200 mg dose of pembrolizumab; the maintenance phase will dose 10 mg/kg muzastotug every 6 weeks (Q6W) plus 400 mg of pembrolizumab Q6W.

Arm B: 20 mg/kg induction dose of muzastotug Q6W plus 400 mg pembrolizumab Q6W for 2 doses; the maintenance phase will dose muzastotug at 15 mg/kg Q6W plus 400 mg pembrolizumab Q6W.

Endpoints: The primary endpoint will be overall response rate (ORR). Secondary endpoints include duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

Qin S, Xu RH, Shen L, Et Al. Subgroup Analysis By Liver Metastasis In The FRESCO Trial Comparing Fruquintinib Versus Placebo Plus Best Supportive Care In Chinese Patients With Metastatic Colorectal Cancer. Onco Targets Ther. 2021;14:4439-; Garcia-Carbonero R, Dasari NA, Eng C, et al. 520P Efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer with and without liver metastasis: A subgroup analysis of the phase III FRESCO-2 trial. Ann Onc 2024;35:S439

(Press release, Adagene, APR 2, 2026, View Source [SID1234664166])