On November 19, 2025 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative, commercial-stage global biotech company dedicated to discovering, developing and commercialising first-in-class and/or best-in-class medicines for autoimmune disease, solid tumors and hematological malignancies indications, reported that at the R&D Day taking place today, it will present the latest data and future plans for three mid/late-stage clinical programs, including ATG-022 (CLDN18.2 antibody-drug conjugate [ADC]), ATG-037 (oral CD73 small molecule inhibitor), and ATG-101 (PD-L1/4-1BB bispecific antibody). The company will also share the latest progress on ATG-125 (B7H3 x PD-L1 bispecific ADC): A B7H3 x PD-L1 targeted therapy featuring "IO + ADC" dual-effect molecules for the treatment of solid tumors and its AnTenGager T-cell engager (TCE) technology platform which incorporates steric hindrance masking, along with updates on several key preclinical programs. In addition, guest expert Prof. Xin Wang, Chief Physician, Drug Clinical Trial Center, National Cancer Center / Cancer Hospital of the Chinese Academy of Medical Sciences, will deliver a keynote session sharing her insights on ATG-022.

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The event will be held today at 14:00 (Beijing Time), both in-person at the Antengene Shanghai office and online via webcast. For further information on how to join the event, please refer to: View Source

1. Building a pipeline of first/best-in-class innovative therapies with strategic focus on four areas

To address major unmet medical needs in the APAC region and globally amid the rapidly evolving innovative drug landscape, Antengene has adopted a forward-looking strategy to build a diverse portfolio covering four major areas – ADCs, immuno-oncology (IO), autoimmune diseases, and TCEs.

ADCs: ATG-022 (CLDN18.2 ADC) is advancing smoothly through clinical development and has generated a steady stream of promising data. In addition, two "IO + ADC" dual-mechanism candidates targeting B7-H3 x PD-L1 and CD24 are progressing well in preclinical development.
IO: ATG-037 (oral CD73 small molecule inhibitor) and ATG-101 (PD-L1/4-1BB bispecific antibody) are progressing smoothly through clinical studies.
Autoimmune diseases: ATG-201 (CD19×CD3 TCE), which is advancing toward clinical studies for the treatment of autoimmune diseases, can mediate complete B cell depletion with reduced risk of cytokine release syndrome (CRS). ATG-207 (undisclosed bifunctional biologics), is a first-in-class preclinical program being developed for T-cell driven autoimmune diseases.
TCEs: Antengene has built a robust portfolio of first/best-in-class programs targeting CD19×CD3, CDH6×CD3, ALPPL2×CD3, LY6G6D×CD3, GPRC5D×CD3, LILRB4×CD3, and FLT3×CD3, offering a wide therapeutic window for addressing unmet clinical needs across autoimmune diseases, solid tumors, and hematologic malignancies.
2. Encouraging data set a solid foundation for further advancement in clinical development

▶ ATG-022 (CLDN18.2 ADC)

Latest data from the Phase I/II CLINCH study: As of November 10, 2025, in patients with moderate to high CLDN18.2 expression (IHC 2+ > 20%), the 2.4 mg/kg dose cohort achieved an objective response rate (ORR) of 40% (12/30), a disease control rate (DCR) of 90% (27/30), and a median overall survival (mOS) of 14.72 months; while the 1.8 mg/kg dose cohort achieved an ORR of 40% (12/30), a DCR of 86.7% (26/30), and a median progression-free survival (mPFS) of 5.45 months. Among patients with low/ultra-low CLDN18.2 expression (IHC 2+ ≤ 20%), those treated at the efficacious dose range of 1.8-2.4 mg/kg achieved an ORR of 28.6% (6/21) and a DCR of 52.4% (11/21). In these results, ATG-022 demonstrated potent antitumor activity in patients with a broad range of CLDN18.2 expression levels.
Broad combinatory potential for front-line treatment: the 1.8 mg/kg cohort demonstrated promising efficacy with only 16.1% of patients experienced grade 3 or higher treatment-related adverse events (TRAEs). This differentiated safety profile uniquely positions ATG-022 as an ADC with best-in-class safety profile and potential to transform first-line standard of care in combination with both immune checkpoint inhibitors (CPIs) and chemotherapy.
Three clinical development pathways: To fully realize the therapeutic potential of its CLDN18.2-targeted therapy ATG-022, Antengene has outlined a clear clinical development roadmap designed to achieve regulatory approval, maximize therapeutic reach, and broaden tumor-type coverage. The strategy includes a near-term approval path through a pivotal Phase III in third and later line gastric cancer patients with moderate to high CLDN18.2 expression; a front-line proof-of-concept Phase II study evaluating ATG-022 in combination with a CPI and the CAPOX regimen, which, if supported by positive results, is expected to advance into a Phase III trial; and A broad indication-expansion effort through the ongoing Phase II study that builds on encouraging activity signals, extending beyond gynecologic tumors to further assess ATG-022 across a wider range of solid tumor types.
▶ ATG-037 (oral CD73 small molecule inhibitor)

Latest data from the Phase I/Ib STAMINA-01 study: As of October 24, 2025, in the subgroup of patients with CPI-resistant melanoma who received the combination regimen (12 patients), the ORR was 33.3%, the DCR was 100%, including 1 complete response (CR) and 3 partial responses (PRs). One of these patients had maintained CR and reported no safety issues despite having been on the treatment for more than two years. In the subgroup of patients with CPI-resistant non-small cell lung cancer (14 patients), the ORR was 21.4%, the DCR was 71.4%, including 3 PRs. These findings suggest that ATG-037 has clinically meaningful therapeutic potential in multiple tumor types, particularly in patients who are CPI-resistant.
Clinical development pathways: existing data show that ATG-037 holds enormous therapeutic potential for the treatment of first-line or CPI-resistant melanoma, with promising potential for expansion into other tumor types. Antengene’s clinical development roadmap for ATG-037 has four main components: 1. combination with CPI for the treatment of CPI-resistant unresectable and metastatic melanoma (second-line treatment); 2. combination with CPI for the first-line treatment of unresectable or metastatic melanoma; 3. active expansion into other tumor types supported by the encouraging proof-of-concept data in CPI-resistant non-small cell lung cancer; 4. explore potential combinations with next-generation CPIs such as PD-1×VEGF bispecific antibody.
▶ ATG-101 (PD-L1/4-1BB bispecific antibody): dose-escalation study of ATG-101 is currently underway in China, the U.S., and Australia, and has already observed favorable safety in varies dosing regimens, thus laying a solid foundation for the future clinical development. One study evaluating ATG-101 in extrapulmonary neuroendocrine carcinoma (EP-NEC) patients will be initiated soon.

3. AnTenGager technology platform: a key driver of innovation

▶ A TCE platform featuring steric hindrance masking: AnTenGager is a proprietary "2+1" second-generation TCE technology platform featuring "2+1" bivalent binding for low-expressing targets, steric hindrance masking, and proprietary CD3 sequences with fast on/off kinetics to minimize CRS and enhance efficacy. These characteristics support the platform’s broad applicability across autoimmune diseases, solid tumors and hematological malignancies indications. Leveraging this platform, Antengene has discovered multiple investigational programs:

ATG-201 (CD19 x CD3 TCE): ATG-201 is a novel "2+1" CD19-targeted T-cell engager developed on the AnTenGagerTM TCE platform for the treatment of B cell related autoimmune diseases. Preclinical data presented at the 2025 American College of Rheumatology (ACR) Annual Meeting showed that in non-human primate (NHP) models, the monkey surrogate of ATG-201 achieved deep and durable depletion of naïve B cells with a favorable safety profile, characterized by only a very mild and transient increase in cytokine levels. The IND-enabling study of ATG-201 has been completed and the IND-submission is under preparation.
ATG-106 (CDH6 x CD3 TCE): A global first-in-class CDH6 x CD3 targeted TCE being developed for the treatment of ovarian cancer and kidney cancer.
ATG-110（LY6G6D x CD3 TCE): A potential global best-in-class LY6G6D x CD3 targeted TCE being developed for the treatment of microsatellite stable colorectal cancer.
ATG-112 (ALPPL2 x CD3 TCE): A global first-in-class ALPPL2 x CD3 targeted TCE being developed for the treatment of gynecologic tumors and lung cancer.
ATG-125 (B7H3 x PD-L1 bispecific ADC): A B7H3 x PD-L1 targeted therapy featuring "IO + ADC" dual-effect molecules for the treatment of solid tumors.
ATG-207 (undisclosed bifunctional biologics): a global first-in-class bifunctional biologic agent being developed for the treatment of T-cell driven autoimmune diseases, a therapeutic area representing a huge unmet clinical need.
Antengene will strive to further accelerate these highly promising clinical and preclinical programs. The company plans to report additional progress of these innovative programs and update the medical community, patients, and investors on future developmental milestones at a series of upcoming top international conferences.

(Press release, Antengene, NOV 19, 2025, View Source [SID1234660099])

On November 19, 2025 Agenus Inc. ("Agenus") (Nasdaq: AGEN), a leader in immuno-oncology, reported it will host its End-of-Year 2025 Stakeholder Webcast on Wednesday, December 3, 2025 at 4:00 p.m. ET. The session will feature leading experts in gastrointestinal oncology and patient advocates discussing progress with the BOT/BAL program, emerging clinical insights, and the evolving treatment landscape for colorectal cancer.

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The session will be moderated by Garo Armen, PhD, Founder, Chairman, and CEO, and will conclude with a live Q&A. Questions can be submitted in advance to [email protected]

Featured Topics and Speakers

Role of Immuno-Oncology in Colorectal Cancer
Christopher Lieu, MD, FASCO, Professor of Medicine; Sohrab Amini, MD, FACS Endowed Chair in Pancreatic Cancer Research; Associate Director for clinical Research, University of Colorado Cancer Center
Dr. Christopher Lieu will discuss the evolving role of immuno-oncology in colorectal cancer, and how expectations for MSS disease are shifting with emerging mechanisms and combination approaches. He will also highlight select clinical insights from his practice, including a notable case that illustrates the potential for deep and durable responses.
Global Phase 3 BATTMAN Study (CO.33) Update
Jonathan Loree, MD; Medical Oncologist, BC Cancer; Associate Professor, University of British Columbia; Senior Investigator, Canadian Cancer Trials Group (CCTG); Co-Chair, NCI Colon Cancer Task Force
Dr. Jonathan Loree will provide an update on the global Phase 3 BATTMAN study, including site engagement, operational readiness, and early feedback from investigators supporting strong trial momentum heading into 2026.
A Caregiver & Physician Perspective: Early-Onset CRC and Paving a New Path Forward
Benny Johnson, DO; Senior Medical Director, Agenus; Former Assistant Professor, GI Medical Oncology MD Anderson Cancer Center
Dr. Johnson will share his family’s experience navigating early-onset colorectal cancer from diagnosis through treatment decision-making, including the choice to participate in a clinical trial evaluating BOT/BAL. Their conversation will highlight the lived realities behind clinical innovation and the importance of expanding patient-centered options for the growing early-onset population, from the perspective of a family impacted by CRC.
Stakeholder Briefing Details:

Registration Link: View Source
Live webcast link will be provided once registration is completed.

Have a Question? Submit them in advance to [email protected]

This session is the third in Agenus’ 2025 Stakeholder Briefing Webcast Series, following the October event highlighting new pan-tumor data from ESMO (Free ESMO Whitepaper) 2025 and perspectives on the French AAC program. Webcasts will resume in 2026, continuing the dialogue on BOT/BAL’s progress and corporate milestones.

(Press release, Agenus, NOV 19, 2025, View Source [SID1234660096])

On November 19, 2025 Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing innovative immuno-oncology technologies addressing difficult to treat cancers, reported it has executed a 4-month extension of its collaboration with The Scripps Research Institute ("Scripps Research") and the lab of Dr. Alexey Stepanov, Institute Investigator at Scripps Research effective November 1, 2025, to advance the development of the Company’s research and development program evaluating the combination of systemic DNase I and CAR T-cell therapies.

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Xenetic’s systemic DNase I candidate, XBIO-015, is currently in preclinical development in combination with CAR-T cell therapy for both hematologic and solid tumors. Studies conducted by Dr. Stepanov and his lab at Scripps Research using lymphoma, metastatic melanoma and leukemia models have shown that co-administration of DNase I with CAR-T cells significantly reduces tumor burden, decreases metastatic lesions, and markedly extends survival compared to CAR-T cell monotherapy. Importantly, systemic DNase I-mediated degrading of neutrophil extracellular traps (NETs) enhances CAR-T cell efficacy, increasing the infiltration of both CAR-T cells and endogenous T cells into tumors and by mitigating the immunosuppressive tumor microenvironment (TME).

"Dr. Stepanov and the Scripps Research team continue to be valued partners, and we are pleased to once again extend our collaboration with them to further explore the full potential of our DNase-based oncology platform. The data generated to date continues to be encouraging and warrants further evaluations. The expertise and dedication of the Scripps Research team to this program further validates our belief in DNase I to improve therapeutic responses in patients undergoing CAR-T cell therapy and we look forward to continued collaboration and innovation together," commented James Parslow, Interim Chief Executive Officer and Chief Financial Officer of Xenetic.

Xenetic continues to advance its DNase-based technology towards Phase 1 clinical development for the treatment of pancreatic carcinoma and other locally advanced or metastatic solid tumors. Preclinical proof-of-concept studies combining DNase I with chemotherapy, immunotherapies, and CAR-T therapy in hematological and solid tumor and metastatic cancer models have been completed. Building on proof-of-concept success, the program has now advanced to mechanism-of-action and translational studies in preparation for a Phase 1 clinical trial.

(Press release, Xenetic Biosciences, NOV 19, 2025, https://ir.xeneticbio.com/news/detail/173/xenetic-biosciences-inc-extends-research-and-development-collaboration-with-institute-investigator-at-scripps-research-to-advance-dnase-platform [SID1234660095])

On November 19, 2025 Tempest Therapeutics, Inc. (Nasdaq: TPST) ("Tempest" or "the Company"), a clinical-stage biotechnology company with a pipeline of targeted and immune-mediated therapeutics to fight cancer, reported that it has entered into definitive agreements to acquire certain dual-targeting chimeric antigen receptor (CAR)-T programs from Factor Bioscience Inc. and its affiliates (collectively, "Factor") in an all-stock transaction (the "Proposed Transaction"). The Proposed Transaction is expected to close in early 2026, subject to necessary stockholder approvals and satisfaction of closing conditions (the "Closing").

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The Proposed Transaction will expand and further diversify Tempest’s existing clinical-stage pipeline, with the acquisition of the first clinical-stage CD19/BCMA parallel structured dual-CAR T specifically designed to target patients with extramedullary disease (EMD), which we are referring to as TPST-2003. In addition, the Company expects that existing cash at Closing and an investment commitment from Factor will support the Company’s planned operations to mid 2027, including through potential key development and data milestones in 2026 and 2027.

Key Takeaways:

Subject to stockholder approval and satisfaction of closing conditions, the Proposed Transaction will both further diversify Tempest’s pipeline and extend the Company’s runway to mid 2027, potentially through value-creating milestones
Tempest plans to pursue business development discussions or an additional financing to advance the pivotal development of amezalpat (TPST-1120) in first-line liver cancer ("HCC")
TPST-2003: dual CD19/BCMA CAR-T program
Phase 1 complete in patients with relapsed multiple myeloma ("rrMM"), with data expected in 2026 and a biologics license application ("BLA") in China planned for 2027
Phase 1 currently enrolling patients with POEMs syndrome, with data expected in 2027 and a BLA in China planned for 2028
Tempest will have global rights to TPST-2003 outside of China, India, Turkey and Russia, and plans to pursue a potential registrational study in rrMM in the U.S. starting in 2027
Data from Chinese pivotal study expected to validate probability of success for Tempest program, and rights will include the right to reference data generated in support of the planned China BLA
Tempest expects a Phase 2 study of TPST-1495 in familial adenomatous polyposis ("FAP") to enroll the first patient in 2026 and to be funded by the National Cancer Institute and operationalized by the Cancer Prevention Clinical Trials Network
Plan to continue the development of additional new preclinical and research-stage pipeline programs:
TPST-2206: dual-targeting CD70/CD70 CAR-T for renal cell carcinoma
TPST-3003: allogeneic dual-targeting CD19/BCMA
TPST-3206: allogeneic dual-targeting CD70/CD70
Tempest will issue 8,268,495 shares of its common stock, par value $0.001 per share ("Common Stock"), to an affiliate of Factor, equal to 65% of the outstanding shares of Common Stock, inclusive of newly issued shares, as of November 19, 2025.
Existing Tempest stockholders will be entitled to receive one (1) common stock warrant for every share of Common Stock held and outstanding at a date immediately prior to the Closing (the "Warrants"). The Warrants will be immediately exercisable with an initial exercise price equal to $18.48 and will expire five years from the issuance date.
Existing cash at Closing and an investment commitment from Factor is expected to provide a runway to mid 2027 and potentially through key data milestones.
Upon Closing, Matt Angel, Ph.D. will become president and chief executive officer ("CEO") of Tempest and current Tempest president and CEO Stephen Brady will become Chairman of the Company’s board of directors.
"The Proposed Transaction will result in an even more diversified portfolio that we believe provides stockholders with new opportunity for value creation and patients with new potential therapies," said Stephen Brady, president and chief executive officer of Tempest. "With the new funding support, Tempest has increased its opportunity to realize potential value creating milestones in the midst of this prolonged challenging market."

Dr. Angel added, "I echo Steve’s sentiments and share in the vision to bring innovative therapies to patients with cancer. I believe there is significant potential to be realized in combining these programs and look forward to working with the Tempest team to bring these programs forward for the benefit of patients."

Matt Angel, Ph.D.

Dr. Matt Angel is an experienced biotechnology executive with expertise in leading lean cell therapy companies. Dr. Angel led Brooklyn Immunotherapeutics (Nasdaq: BTX) as CEO from 2022-2023, successfully restructuring the company and extending the company’s runway in a challenging market environment. Dr. Angel has led Factor Bioscience Inc. as co-founder and CEO since 2011 and is co-founder of cell therapy companies Novellus Therapeutics (founded 2014; sold 2021) and Exacis Biotherapeutics (founded 2020; sold 2023). Dr. Angel has deep expertise in cell therapy development and intellectual property protection and licensing. Dr. Angel is also experienced in assembling and managing multidisciplinary teams. A pioneer in cell engineering technology, Dr. Angel is a prolific inventor with more than 150 patents covering mRNA, nucleic acid delivery, gene editing, and cell reprogramming technologies. Dr. Angel received his Ph.D. from the Massachusetts Institute of Technology, where he published seminal discoveries in the then-nascent field of mRNA.

Approvals and Timing

The board of directors of Tempest has unanimously approved the Proposed Transaction and intends to recommend that Tempest stockholders vote to adopt the asset purchase agreement and the related issuance of Common Stock with respect to the Proposed Transaction at a meeting of stockholders.

The Proposed Transaction is conditioned upon approval of the holders of a majority of the outstanding shares of Common Stock of Tempest entitled to vote to adopt the asset purchase agreement with respect to the Proposed Transaction.

Completion of the transaction is expected in early 2026, subject to the approval of Tempest stockholders and the satisfaction of other customary closing conditions.

Advisors

MTS Health Partners, L.P. is serving as financial advisor to Tempest, and Cooley LLP is serving as legal advisor. In addition, MTS Securities, LLC (an affiliate of MTS Health Partners, L.P.) provided an opinion to the board of directors of Tempest regarding the fairness of the purchase price to be paid by Tempest to Factor in connection with the Proposed Transaction, subject to the qualifications and limitations set forth therein.

(Press release, Tempest Therapeutics, NOV 19, 2025, View Source [SID1234660094])

On November 19, 2025 Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, reported that it has completed the planned enrollment of 50 patients necessary for the interim analysis in its 80 patient confirmatory Phase 3 double-blind, placebo-controlled study evaluating HyBryte (synthetic hypericin) in the treatment of cutaneous T-cell lymphoma (CTCL). The confirmatory Phase 3 study (Fluorescent Light Activated Synthetic Hypericin 2, FLASH2), builds on the previous statistically significant Phase 3 (FLASH) study, as well as a recent successful comparative study (HPN-CTCL-04) and an ongoing investigator-initiated study .

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"We are pleased to have reached this important milestone in patient enrollment consistent with our timelines for the FLASH2 study," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "With 50 patients enrolled, the planned interim analysis will occur in the second quarter of 2026. FLASH2 was designed as a highly powered confirmatory study with an anticipated overall blinded study response rate of 25% (based on the conservative assumptions of a 40% response rate in the HyBryte arm and a 10% response rate in the placebo arm through 18 weeks). When considering all patients that have completed the treatment phase of the study to date, our overall blinded study response rate is 48%. We look forward to completing this study on schedule with topline results in the second half of 2026."

"The findings so far are consistent with the ongoing open-label, investigator-initiated study being conducted at my institution where HyBryte has demonstrated a response rate of 75% after 18 weeks of treatment," stated Ellen Kim, MD, Director, Penn Cutaneous Lymphoma Program, Vice Chair of Clinical Operations, Dermatology Department, Professor of Dermatology at the Hospital of the University of Pennsylvania, and Lead Investigator of the FLASH2 study. "The benign safety profile we observed in the first FLASH study, as well as in the ongoing investigator-initiated study, continues to be observed in FLASH2, as evidenced by the recently achieved safety review milestone."

FLASH2 is a randomized, double-blind, placebo-controlled, multicenter study that is enrolling approximately 80 subjects with early-stage CTCL. The study Data Monitoring Committee (DMC) is empowered to conduct one formal Interim Analysis when approximately 60% (n = 48) of the total patients have completed the primary endpoint evaluation (i.e., Week 18 or before). The study replicates the double-blind, placebo-controlled design used in the first successful Phase 3 FLASH study that consisted of three 6-week treatment cycles (18 weeks total), with the primary efficacy assessment occurring at the end of the initial 6-week double-blind, placebo-controlled treatment cycle (Cycle 1). However, this second study extends the double-blind, placebo-controlled assessment to 18 weeks of continuous treatment (no "between-Cycle" treatment breaks) with the primary endpoint assessment occurring at the end of the 18-week timepoint. In the first Phase 3 study, a treatment response of 49% (p<0.0001 vs patients receiving placebo in Cycle 1) was observed in patients completing 18 weeks (3 cycles) of therapy. In this second study, all important clinical study design components remain the same as in the first FLASH study, including the primary endpoint and key inclusion-exclusion criteria. The extended treatment for a continuous 18 weeks in a single cycle is expected to statistically demonstrate the effect of HyBryte over a more prolonged, "real world" treatment course.

About HyBryte

HyBryte (research name SGX301) is a novel, first-in-class, photodynamic therapy utilizing safe, visible light for activation. The active ingredient in HyBryte is synthetic hypericin, a potent photosensitizer that is topically applied to skin lesions that is taken up by the malignant T-cells, and then activated by safe, visible light approximately 24 hours later. The use of visible light in the red-yellow spectrum has the advantage of penetrating more deeply into the skin (much more so than ultraviolet light) and therefore potentially treating deeper skin disease and thicker plaques and lesions. This treatment approach avoids the risk of secondary malignancies (including melanoma) inherent with the frequently employed DNA-damaging drugs and other phototherapy that are dependent on ultraviolet exposure. Combined with photoactivation, hypericin has demonstrated significant anti-proliferative effects on activated normal human lymphoid cells and inhibited growth of malignant T-cells isolated from CTCL patients. In a published Phase 2 clinical study in CTCL, patients experienced a statistically significant (p=0.04) improvement with topical hypericin treatment whereas the placebo was ineffective. HyBryte has received orphan drug and fast track designations from the FDA, as well as orphan designation from the European Medicines Agency (EMA).

The published Phase 3 FLASH trial enrolled a total of 169 patients (166 evaluable) with Stage IA, IB or IIA CTCL. The trial consisted of three treatment cycles. Treatments were administered twice weekly for the first 6 weeks and treatment response was determined at the end of the 8th week of each cycle. In the first double-blind treatment cycle (Cycle 1), 116 patients received HyBryte treatment (0.25% synthetic hypericin) and 50 received placebo treatment of their index lesions. A total of 16% of the patients receiving HyBryte achieved at least a 50% reduction in their lesions (graded using a standard measurement of dermatologic lesions, the modified Composite Assessment of Index Lesion Severity [mCAILS] score) compared to only 4% of patients in the placebo group at 8 weeks (p=0.04) during the first treatment cycle (primary endpoint). HyBryte treatment in this cycle was safe and well tolerated.

In the second open-label treatment cycle (Cycle 2), all patients received HyBryte treatment of their index lesions. Evaluation of 155 patients in this cycle (110 receiving 12 weeks of HyBryte treatment and 45 receiving 6 weeks of placebo treatment followed by 6 weeks of HyBryte treatment), demonstrated that the response rate among the 12-week treatment group was 40% (p<0.0001 vs the placebo treatment rate in Cycle 1). Comparison of the 12-week and 6-week treatment responses also revealed a statistically significant improvement (p<0.0001) between the two timepoints, indicating that continued treatment results in better outcomes. HyBryte continued to be safe and well tolerated. Additional analyses also indicated that HyBryte is equally effective in treating both plaque (response 42%, p<0.0001 relative to placebo treatment in Cycle 1) and patch (response 37%, p=0.0009 relative to placebo treatment in Cycle 1) lesions of CTCL, a particularly relevant finding given the historical difficulty in treating plaque lesions.

The third (optional) treatment cycle (Cycle 3) was focused on safety and all patients could elect to receive HyBryte treatment of all their lesions. Of note, 66% of patients elected to continue with this optional compassionate use / safety cycle of the study. Of the subset of patients that received HyBryte throughout all 3 cycles of treatment, 49% of them demonstrated a positive treatment response (p<0.0001 vs patients receiving placebo in Cycle 1). Moreover, in a subset of patients evaluated in this cycle, it was demonstrated that HyBryte is not systemically available, consistent with the general safety of this topical product observed to date. At the end of Cycle 3, HyBryte continued to be well tolerated despite extended and increased use of the product to treat multiple lesions.

Overall safety of HyBryte is a critical attribute of this treatment and was monitored throughout the three treatment cycles (Cycles 1, 2 and 3) and the 6-month follow-up period. HyBryte’s mechanism of action is not associated with DNA damage, making it a safer alternative than currently available therapies, all of which are associated with significant, and sometimes fatal, side effects. Predominantly these include the risk of melanoma and other malignancies, as well as the risk of significant skin damage and premature skin aging. Currently available treatments are only approved in the context of previous treatment failure with other modalities and there is no approved front-line therapy available. Within this landscape, treatment of CTCL is strongly motivated by the safety risk of each product. HyBryte potentially represents the safest available efficacious treatment for CTCL. With very limited systemic absorption, a compound that is not mutagenic and a light source that is not carcinogenic, there is no evidence to date of any potential safety issues.

Following the first Phase 3 study of HyBryte for the treatment of CTCL, the FDA and the EMA indicated that they would require a second successful Phase 3 trial to support marketing approval. With agreement from the EMA on the key design components, the second, confirmatory study, called FLASH2, has successfully achieved its first safety review milestone with a pre-specified, blinded interim analysis expected to be completed in 2Q2026. This study is a randomized, double-blind, placebo-controlled, multicenter study that will enroll approximately 80 subjects with early-stage CTCL. The FLASH2 study replicates the double-blind, placebo-controlled design used in the first successful Phase 3 FLASH study that consisted of three 6-week treatment cycles (18 weeks total), with the primary efficacy assessment occurring at the end of the initial 6-week double-blind, placebo-controlled treatment cycle (Cycle 1). However, this second study extends the double-blind, placebo-controlled assessment to 18 weeks of continuous treatment (no "between-Cycle" treatment breaks) with the primary endpoint assessment occurring at the end of the 18-week timepoint. In the first Phase 3 study, a treatment response of 49% (p<0.0001 vs patients receiving placebo in Cycle 1) was observed in patients completing 18 weeks (3 cycles) of therapy. In this second study, all important clinical study design components remain the same as in the first FLASH study, including the primary endpoint and key inclusion-exclusion criteria. The extended treatment for a continuous 18 weeks in a single cycle is expected to statistically demonstrate HyBryte’s increased effect over a more prolonged, "real world" treatment course. Given the extensive engagement with the CTCL community, the esteemed Medical Advisory Board and the previous trial experience with this disease, accelerated enrollment in support of this study is anticipated, including the potential to enroll previously identified and treated HyBryte patients from the FLASH study. Discussions with the FDA on an appropriate study design remain ongoing. While collaborative, the agency has expressed a preference for a longer duration comparative study over a placebo-controlled trial. Given the shorter time to potential commercial revenue and the similar trial design to the first FLASH study afforded by the EMA accepted protocol, this study was initiated. At the same time, discussions with the FDA will continue on potential modifications to the development path to adequately address their feedback.

Additional supportive studies have demonstrated the utility of longer treatment times (Study RW-HPN-MF-01), the lack of significant systemic exposure to hypericin after topical application (Study HPN-CTCL-02) and its relative efficacy and tolerability compared to Valchlor (Study HPN-CTCL-04).

In addition, the FDA awarded an Orphan Products Development grant to support the investigator-initiated study evaluation of HyBryte for expanded treatment in patients with early-stage CTCL, including in the home use setting. The grant, totaling $2.6 million over 4 years, was awarded to the University of Pennsylvania that was a leading enroller in the Phase 3 FLASH study.

About Cutaneous T-Cell Lymphoma (CTCL)

CTCL is a class of non-Hodgkin’s lymphoma (NHL), a type of cancer of the white blood cells that are an integral part of the immune system. Unlike most NHLs which generally involve B-cell lymphocytes (involved in producing antibodies), CTCL is caused by an expansion of malignant T-cell lymphocytes (involved in cell-mediated immunity) normally programmed to migrate to the skin. These malignant cells migrate to the skin where they form various lesions, typically beginning as patches and may progress to raised plaques and tumors. Mortality is related to the stage of CTCL, with median survival generally ranging from about 12 years in the early stages to only 2.5 years when the disease has advanced. There is currently no cure for CTCL. Typically, CTCL lesions are treated and regress but usually return either in the same part of the body or in new areas.

CTCL constitutes a rare group of NHLs, occurring in about 4% of the more than 1.7 million individuals living with the disease in the U.S. and Europe (European Union and United Kingdom). It is estimated, based upon review of historic published studies and reports and an interpolation of data on the incidence of CTCL that it affects approximately 31,000 individuals in the U.S. (based on SEER [Surveillance, Epidemiology, and End Results] data, with approximately 3,200 new cases seen annually) and approximately 38,000 individuals in Europe (based on ECIS [European Cancer Information System] prevalence estimates, with approximately 3,800 new cases annually).

(Press release, Soligenix, NOV 19, 2025, View Source [SID1234660093])