On April 3, 2024 Daiichi Sankyo (TSE: 4568) and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the first patient has been dosed in the REJOICE-Ovarian01 Phase 2/3 trial evaluating the efficacy and safety of investigational raludotatug deruxtecan (R-DXd) in patients with platinum-resistant ovarian cancer (Press release, Merck & Co, APR 3, 2024, View Source [SID1234641750]). The Phase 2 portion of the trial will be conducted to identify the dose of raludotatug deruxtecan to be used in the Phase 3 part of the trial, which will evaluate raludotatug deruxtecan versus investigator’s choice of chemotherapy.

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Raludotatug deruxtecan is an investigational specifically engineered potential first-in-class CDH6 directed DXd antibody-drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed with Merck.

Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens.1 The median overall survival for advanced ovarian cancer following recurrence is approximately two years, with a five-year survival rate of less than 30%.2,3 Up to 85% of advanced ovarian tumors have overexpression of CDH6, which is associated with poor prognosis.4,5

The initiation of REJOICE-Ovarian01 is based on results from an ongoing Phase 1 trial of raludotatug deruxtecan presented at the European Society for Medical Oncology Congress 2023 with a subgroup analysis presented at the Society for Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer.

"Raludotatug deruxtecan has shown promising activity in a Phase 1 trial of patients with advanced ovarian cancer," said Mark Rutstein, MD, global head, oncology clinical development, Daiichi Sankyo. "The REJOICE-Ovarian01 trial, which is our first trial initiation for raludotatug deruxtecan in collaboration with Merck, will evaluate the efficacy of this CDH6 directed DXd antibody-drug conjugate versus investigator’s choice of chemotherapy in patients with platinum-resistant ovarian cancer."

"The prognosis for the majority of patients diagnosed with advanced ovarian cancer is bleak, with a low five-year survival rate, underscoring the critical need for the development of innovative and effective therapies," said Marjorie Green, MD, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. "We look forward to working with our colleagues at Daiichi Sankyo to further evaluate the potential of raludotatug deruxtecan to provide a new treatment option for patients with platinum-resistant ovarian cancer."

About the REJOICE-Ovarian01 trial

REJOICE-Ovarian01 is a global, multicenter, randomized, open-label Phase 2/3 trial evaluating the efficacy and safety of investigational raludotatug deruxtecan (R-DXd) in patients with platinum-resistant, high-grade ovarian cancer, including primary peritoneal or fallopian tube cancer, who received at least one and no more than three prior systemic lines of anticancer therapy, including prior treatment with mirvetuximab soravtansine for those with documented high-folate receptor alpha expression.

The Phase 2 part of REJOICE-Ovarian01 will assess the safety and tolerability of three doses of raludotatug deruxtecan (4.8 mg/kg, 5.6 mg/kg, or 6.4 mg/kg) to identify the recommended dose for the Phase 3 part of the trial. The primary endpoint of the Phase 2 part of the trial is objective response rate (ORR) as assessed by blinded independent central review (BICR). Secondary endpoints include ORR as assessed by investigator, duration of response (DoR), progression free survival (PFS) and disease control rate (DCR) – all assessed by both BICR and investigator – and overall survival (OS).

The Phase 3 part of REJOICE-Ovarian01 will assess the efficacy and safety of raludotatug deruxtecan at the selected dose compared to investigator’s choice of chemotherapy (paclitaxel, pegylated liposomal doxorubicin, gemcitabine, or topotecan). The dual primary endpoints of the Phase 3 part of the trial are ORR and PFS as assessed by BICR. Secondary endpoints include PFS and ORR as assessed by investigator, DoR and DCR as assessed by both BICR and investigator, and OS. Pharmacokinetic and biomarker endpoints also will be assessed in both parts of the trial.

The trial is expected to enroll approximately 650 patients across Asia, Europe, North America and South America. For more information, please visit ClinicalTrials.gov.

About ovarian cancer

More than 324,000 women were diagnosed with ovarian cancer worldwide in 2022.6,7 Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens.1 The median overall survival for advanced ovarian cancer following recurrence is approximately two years, with a five-year survival rate of less than 30%.2,3 For patients that develop resistance to platinum-based chemotherapy, treatment options are limited.8

The introduction of targeted therapies has expanded treatment options and improved survival outcomes for some patients with ovarian cancer, but additional options are needed for patients with tumors that progress on available medicines.9

About CDH6

CDH6 (human cadherin-6) is a cadherin family protein overexpressed in several cancers, including ovarian tumors.4 An estimated 65% to 85% of patients with ovarian cancer have tumors that express CDH6, which is associated with poor prognosis.4,5 There is currently no CDH6 directed therapy approved for treatment of any cancer.

About raludotatug deruxtecan

Raludotatug deruxtecan (R-DXd) is an investigational, potential first-in-class CDH6 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, raludotatug deruxtecan is comprised of a humanized anti-CDH6 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

In addition to the REJOICE-Ovarian01 trial, raludotatug deruxtecan is being evaluated in a Phase 1 trial in advanced ovarian cancer as part of a strategic collaboration with Sarah Cannon Research Institute (SCRI) with study operational oversight and delivery provided through SCRI’s early phase oncology clinical research organization, SCRI Development Innovations in Nashville, TN.

About the Daiichi Sankyo and Merck collaboration

Daiichi Sankyo and Merck (known as MSD outside of the United States and Canada) entered into a global collaboration in October 2023 to jointly develop and commercialize patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd), except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply.

About the DXd ADC portfolio of Daiichi Sankyo

The DXd ADC portfolio of Daiichi Sankyo currently consists of six ADCs in clinical development across multiple types of cancer. ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo.

Designed using Daiichi Sankyo’s proprietary DXd ADC Technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan and DS-3939 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.

On April 3, 2024 VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease, reported that David E. Anderson, Ph.D., VBI’s Chief Scientific Officer, will present early tumor response data from the ongoing Phase 2b study of VBI-1901, VBI’s cancer vaccine immunotherapeutic candidate, in recurrent glioblastoma (rGBM) at the World Vaccine Congress Washington at 1:10pm ET on April 3, 2024 (Press release, VBI Vaccines, APR 3, 2024, View Source [SID1234641749]). The multi-center, randomized, controlled, open-label study has been designed to evaluate overall survival, tumor response rates, and safety and tolerability of VBI-1901 as a monotherapy in rGBM patients.

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Dr. Anderson commented: "In recurrent GBM, tumors typically double or triple in size within six weeks, with no effective treatments available to improve survival. Early indications from this ongoing study suggest tumor growth behavior in-line with expectations for both the standard-of-care arm and the VBI-1901 arm, based on positive data seen from the Phase 1/2a study. While early, I am very excited by these results and hope to see the trends continue to confirm the results seen in earlier studies, where VBI-1901 improved median overall survival by ~5 months compared to historical controls – ~13 months vs. ~8 months1 – and achieved a 44% DCR."

Based on the data seen in the Phase 1/2a study of VBI-1901 in rGBM patients, the FDA granted Fast Track Designation in June 2021 and Orphan Drug Designation in June 2022.

Dr. Anderson’s presentation will be archived on the Events/Presentations page in the Investors section of VBI’s website.

Phase 2b Data Highlights

As of March 22, 2024, 17 patients have been randomized 1:1 to either the active, VBI-1901 treatment arm, or to the control, standard-of-care treatment arm (SoC).

Active Study Arm: VBI-1901 + Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
9 patients have been randomized and 5 of those patients are currently evaluable for tumor response assessment (n=5)
2 stable disease (SD) have been observed in the VBI-1901 arm to-date
40% (n=2/5) early disease control rate achieved
Control Study Arm: Standard-of-Care (SoC) Therapy – Carmustine or Lomustine
8 patients have been randomized and 6 of those patients are currently evaluable for tumor response assessment (n=6)
No tumor responses have been observed in the SoC arm
0% (n=0/6) disease control rate
All evaluable patients have experienced tumor progression and have been taken off study protocol
Phase 2b Patient Enrollment Update

14 leading neuro-oncology centers are actively recruiting patients across the United States
2 new clinical sites were activated in March 2024, with a third site expected to come online in April
Patient enrollment in Q1 2024 was double the enrollment rate observed in Q4 2023
Phase 1/2a Study Data Highlights – VBI-1901 10µg + GM-CSF Study Arms

(n=16)

44% disease control rate achieved (n=7/16) – disease control rate is defined as stable disease (SD) + partial tumor response (PR) + complete tumor response (CR)
2 partial responses (PR) were observed – 1 patient was on treatment for more than 28 months (2.33 years), surviving at least 40 months (3.33 years) as of August 1, 2023, with a maximum tumor reduction of 93% relative to baseline
5 additional patients demonstrated stable disease (SD) for a sustained period of time
All patients with a tumor response (PR or SD) (n=7/16) reached a minimum survival of 12 months
Median overall survival (mOS) was 12.9 months, comparing favorably to 8-month mOS for monotherapy standard-of-care1
Phase 2b Study Design

Multi-center, randomized, controlled, open-label study in up to 60 patients with first recurrent GBM

Patients will be randomized in a 1:1 ratio across two study arms:
Intradermal VBI-1901 + GM-CSF: 10 µg dose every 4 weeks until clinical disease progression
Monotherapy standard-of-care: either intravenous carmustine or oral lomustine, every 6 weeks until disease progression or intolerable toxicity
Endpoints include:
Safety and tolerability
Overall survival (OS) – median and overall
Tumor response rate (TRR)
Progression-free survival (PFS)
Immunologic responses
Reduction in corticosteroid use relative to baseline
Change in quality of life compared to baseline
The U.S. Food and Drug Administration (FDA) has considered demonstration of a statistically significant improvement in overall survival relative to a randomized control arm to be clinically significant and has recognized this as criteria to support the approval of new oncology drugs.2

For more information about the Phase 2b study, visit clinicaltrials.gov and reference trial identifier: NCT03382977.

About GBM and VBI-1901

Scientific literature suggests CMV infection is prevalent in multiple solid tumors, including glioblastoma (GBM). GBM is among the most common and aggressive malignant primary brain tumors in humans. In the U.S. alone, 14,000 new cases are diagnosed each year. The current standard of care for treating GBM is surgical resection, followed by radiation and chemotherapy. Even with aggressive treatment, GBM progresses rapidly and has a high mortality.

VBI-1901 is a novel cancer vaccine immunotherapeutic candidate developed using VBI’s enveloped virus-like particle (eVLP) technology to target two highly immunogenic cytomegalovirus (CMV) antigens, gB and pp65. The FDA has granted VBI-1901 Fast Track Designation and Orphan Drug Designation for the treatment of recurrent glioblastoma. These designations are intended to provide certain benefits to drug developers, including more frequent meetings with the FDA, and Accelerated Approval and Priority Review, if relevant criteria are met, among other benefits.

On April 3, 2024 TRACON Pharmaceuticals (NASDAQ: TCON), a clinical stage biopharmaceutical company utilizing a cost-efficient, CRO-independent Product Development Platform (PDP) to advance its pipeline of novel targeted cancer therapeutics and to partner with other life science companies, reported the independent data monitoring committee (IDMC), following a review of ongoing safety and efficacy data on April 2, recommended the ENVASARC Phase 2 pivotal trial continue as planned (Press release, Tracon Pharmaceuticals, APR 3, 2024, View Source [SID1234641748]). The ENVASARC Phase 2 pivotal trial completed enrollment in March 2024 with a total of 82 evaluable patients in cohort C of treatment with single agent envafolimab at 600 mg SQ every three weeks and final data are expected in the third quarter of 2024.

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The IDMC reviewed interim safety and efficacy data from 73 patients enrolled into cohort C who had the opportunity to complete two on-treatment scans (a minimum of 12 weeks of treatment). The objective response rate (ORR) is currently 11% by investigator review and the confirmed ORR by blinded independent central review (BICR) is currently 5.5% (four patients). Median duration of response by BICR is greater than six months. Envafolimab has been well tolerated without the development of a single drug-related serious adverse event of grade 3 or higher. The primary endpoint of the study is achievement of an objective response in nine of 82 patients (11%) treated with envafolimab by BICR and median duration of response of greater than six months is a key secondary endpoint.

"Subcutaneous envafolimab has been generally well tolerated and continues to demonstrate durable single agent activity in a subset of these sarcoma patients," said James Freddo, M.D., TRACON’s Chief Medical Officer. "An additional five objective responses confirmed by central review are needed to achieve our goal in the 82 patient cohort of single agent envafolimab treatment."

"We believe that achievement of the primary endpoint in the ENVASARC trial would position envafolimab to become a potentially compelling treatment option for patients with the refractory sarcoma subtypes of UPS and MFS," said Charles Theuer, M.D., Ph.D., TRACON’s Chief Executive Officer

About ENVASARC (NCT04480502)

The ENVASARC pivotal trial is a multicenter, open label, randomized, non-comparative, parallel cohort study at 30 top cancer centers in the United States and the United Kingdom that began dosing in December 2020. The primary endpoint is ORR by blinded central review of nine responses in cohort C of 82 evaluable patients with duration of response a key secondary endpoint. The trial is fully enrolled and the primary endpoint will continue to be evaluated.

On April 3, 2024 TAE Life Sciences, a pioneer in advancing Boron Neutron Capture Therapy (BNCT) for cancer treatment, reported the successful completion of acceptance testing and regulatory registration inspection of its accelerator- based neutron beam system (NBS), marking a significant milestone in BNCT global market adoption (Press release, TAE Life Sciences, APR 3, 2024, View Source [SID1234641747]). Developed and manufactured in the United States, TAE Life Sciences’ NBS has met all specifications outlined by Neuboron Medical and the local regulatory body, enabling human BNCT clinical trials to begin this month in China.

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The completion of acceptance testing underscores TAE Life Sciences’ commitment to international safety and efficacy standards, making it the first US company to have its system achieve such recognition. This major technological progress demonstrates how TAE Life Sciences has solidified its leading position in the growing field of BNCT. As the company progresses in establishing Alphabeam BNCT sites worldwide, collaborating with Neuboron to provide them with a Neutron Beam System has paved a distinctive pathway into the Chinese market.

"We worked closely with Neuboron to ensure our accelerator-based NBS precisely delivered the results required for BNCT and are thrilled to have successfully completed acceptance testing and regulatory inspection," stated Rob Hill, CEO at TAE Life Sciences. "This milestone not only demonstrates our dedication to delivering cutting-edge cancer treatment solutions, but also signifies our ability to meet rigorous international standards."

Additionally, the Beijing Institute of Medical Device Testing has completed registration testing of the full Neuboron Medical’s NeuPex AB-BNCT system, which includes TAE Life Science’s NBS. This milestone marks a significant regulatory approval step, enabling Neuboron to move forward with clinical trials in China. Neuboron will commence clinical trials at Xiamen Humanity Hospital.

The latest market analysis report by Intel Market Research forecasts robust growth in the BNCT market, with global revenues projected to reach $2.2 billion by 2030. TAE Life Sciences, alongside industry leaders such as Neuboron, Sumitomo, and others, is poised to play a pivotal role in driving this exponential growth.

As the BNCT market continues to expand, TAE Life Sciences remains at the forefront of innovation, delivering transformative solutions to cancer patients worldwide.

For more information about TAE Life Sciences, Alphabeam, and the company’s proprietary boronated BNCT drugs, please visit taelifesciences.com.

For more information about Neuboron and its technologies, please visit neuboron.com/.

On April 3, 2024 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 received agreement from the European Medicines Agency (EMA) on the key design components of a confirmatory Phase 3 placebo-controlled study evaluating the safety and efficacy of HyBryte (synthetic hypericin) in the treatment of cutaneous T-cell lymphoma (CTCL) patients with early-stage disease (Press release, Soligenix, APR 3, 2024, View Source [SID1234641746]). This confirmatory 18-week study is expected to enroll approximately 80 patients in the United States and Europe and is targeted to begin patient enrollment by the end of 2024 with top-line results anticipated in the second half of 2026.

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The confirmatory study, called FLASH2 (Fluorescent Light Activated Synthetic Hypericin 2), 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, the 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.

"In treating CTCL, which is a chronic cancer with no cure, long-term safety is a strong driver of treatment choice. Most current treatment options for CTCL are associated with significant safety concerns, including black-box warnings," stated Brian Poligone, MD, PhD, Director of the Rochester Skin Lymphoma Medical Group, Fairport, NY. "Clinical studies with HyBryte have demonstrated strong and rapid efficacy with a very benign safety profile, with broad applicability across different lesion types, different skin tones and different disease stages. I know I can speak for my colleagues that have been involved with these studies when I say that the data generated to date has been extremely compelling. This second study is very similar to the first FLASH study, and should build on these compelling data, while allowing us to more closely treat as we would in a ‘real world’ setting. We believe the outcome of this trial will further validate the utility of HyBryte in early-stage CTCL and we look forward to participating in this important study."

"With its chronic course and major impact on patient quality of life, CTCL is an orphan disease in urgent need of additional treatment options that are well-tolerated and safe over the long term," stated Christopher Schaber, PhD, President and Chief Executive Officer of Soligenix. "Studies to date have indicated a substantial increase in efficacy with longer treatment and similar performance against both patch and plaque lesions. These results are derived from one of the largest studies ever conducted in CTCL, and we believe this second study will both substantiate and improve upon these results. Given our extensive engagement with the CTCL community, our esteemed Medical Advisory Board and our previous trial experience with this disease, we anticipate being able to accelerate enrollment in support of this study, 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, we will initiate that study. At the same time, we will continue discussions with the FDA on modifying the development path to adequately address their feedback."

The confirmatory Phase 3, randomized, double-blind, placebo-controlled, multicenter study includes approximately 80 subjects with early-stage CTCL. It will evaluate the efficacy and safety of HyBryte topically applied to CTCL lesions twice weekly for 18 weeks, with each application followed 21 (±3) hours later by the administration of safe, visible light at a wavelength of 500 to 650 nm. The light will be administered starting at 6 J/cm2 twice weekly. This will be increased upwards by 2 J/cm2 until: 1) the patient experiences a Grade 1 erythema, 2) the patient reaches the maximum dose of 30 J/cm2, or 3) the patient cannot tolerate the treatment time, whichever comes first. All of the patient’s lesions that are readily available for exposure to the visible light source will be treated and 3 to 5 index lesions in each patient will be prospectively identified and indexed for the modified composite assessment of index lesions severity (mCAILS) evaluation prior to randomization (baseline). The primary efficacy endpoint will be assessed on the percent of patients in each of the two treatment groups (i.e., HyBryte and placebo) achieving a Partial or Complete Response (yes/no) of the treated lesions defined as a ≥ 50% reduction in the total mCAILS score for the 3-5 index lesions following 18 weeks of treatment compared to the total mCAILS score at baseline. Other secondary measures will assess treatment response (including duration), degree of improvement, time to relapse and safety. Following treatment, all patients will be followed every 4 weeks for a total of 12 weeks (through Week 30). The Data Monitoring Committee (DMC) will conduct one (1) interim analysis when approximately 60% of the total subjects have completed the primary endpoint evaluation. The primary efficacy endpoint and the key safety endpoints will be analyzed. A sample size recalculation may be performed after examining the assumptions or the trial halted for either futility, safety concerns, or overwhelming efficacy. Soligenix, participating clinical investigators, and any personnel involved in trial conduct will remain blinded to study treatment until completion of the trial.

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 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 CAILS 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 groups also revealed a statistically significant improvement (p<0.0001) between the two groups, 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 in particular.

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.

The Phase 3 FLASH study was partially funded by the National Cancer Institute via a Phase II SBIR grant (#1R44CA210848-01A1) awarded to Soligenix, Inc. In addition, the FDA awarded an Orphan Products Development grant to support the 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 1.2 million individuals living with the disease. 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 30,000 individuals in the U.S. (based on SEER data, with approximately 3,200 new cases seen annually) and over 20,000 individuals in Europe (based on 5-year prevalence data, with approximately 5,600 new cases annually).