Mechlorethamine Hydrochloride

引言化疗 (Chemotherapy)，这个词对许多人来说，既是希望的象征，也是恐惧的源头。作为对抗癌症的“焦土政策”，它用强大的化学武器无差别地攻击快速分裂的细胞，力图将癌细胞赶尽杀绝。我们歌颂它挽救了无数生命，但也深知其沉重的副作用——脱发、恶心、疲惫……这些是身体发出的短期警报。然而，在这场战争的硝烟散去多年之后，当患者重返正常生活，那些曾经“躺枪”的健康细胞，尤其是我们体内不断更新的血液细胞，它们的命运又将如何？它们是否也在这场战役中留下了不为人知的“战争创伤”？这些创伤是会随着时间愈合，还是会像一枚枚定时炸弹，埋下未来健康风险的隐患？长期以来，这些问题更像是一种基于临床观察的模糊推断，缺乏微观层面上的确凿证据。7月1日，《Nature Genetics》上的重磅研究“The long-term effects of chemotherapy on normal blood cells”，首次为我们揭开了这个“潘多拉魔盒”的一角。研究人员以前所未有的精度，深入到单个血细胞的基因组中，像法医一样，解读着化疗留下的每一个分子层面的“伤疤”。这项研究不仅证实了我们的担忧，更以惊人的细节，描绘出了一幅化疗后正常血细胞世界的“患者编年史”。生命之河的源头：我们血液世界的秘密在深入这场关于“化疗伤痕”的探索之前，我们必须先了解我们身体里那条永不停歇的“生命之河”——血液——是如何运作的。这条河流的源头，深藏于我们的骨髓之中，那里居住着一群神奇的“始祖细胞”，它们被称为造血干祖细胞 (Hematopoietic stem and progenitor cells, HSPCs)。这些HSPCs是我们所有血细胞的共同祖先，包括负责运输氧气的红细胞、构成免疫防线的白细胞（如淋巴细胞、单核细胞等）以及参与凝血的血小板。HSPCs拥有一项非凡的能力：自我更新与分化。它们既能复制出更多的自己，维持“源头”的永不枯竭；也能分化成各种功能各异的成熟血细胞，补充到血液循环中。这个过程周而复始，确保我们生命活动的正常运转。然而，细胞的每一次分裂，都伴随着微小的风险。细胞内的DNA在复制过程中，偶尔会出错，就像抄写员在抄写一部鸿篇巨著时，难免会写错一两个字。这种DNA序列上的永久性改变，就是体细胞突变 (somatic mutation)。这些突变大多是无害的，但它们会随着年龄的增长而不断累积。研究早已揭示，这是一个相当稳定的过程。一个健康成年人的HSPCs，平均每年会稳定地增加大约18个单碱基替换 (Single-Base Substitution, SBS)，这是最常见的突变类型。这意味着，一位健康的80岁老人，其单个HSPC中大约携带着1500个这样的“岁月印记”。这个数字，就像一把衡量细胞“生理年龄”的尺子，为我们提供了一个至关重要的基准。有了这把尺子，研究人员便可以开始回答那个核心问题：当化疗这股强大的外部力量介入时，这把尺子上的刻度，会发生怎样的剧变？基因组考古学：巧妙的设计揭示细胞的过往想要知道化疗究竟做了什么，研究人员必须像考古学家一样，发掘并解读细胞基因组中埋藏的历史信息。他们采用了一种极其巧妙的研究策略。首先，他们招募了一个特殊的群体：一共23位曾接受过化疗的癌症患者，他们的年龄跨度极大，从3岁到80岁不等。这些患者所患的癌症类型多样，包括结直肠癌、淋巴瘤、白血病等；他们接受的化疗方案也五花八门，涵盖了我们熟知的几乎所有主要化疗药物类别，例如烷化剂 (alkylating agents)、铂类药物 (platinum compounds)、抗代谢药物 (antimetabolites)等，总共涉及21种不同的药物。与此同时，他们还招募了9位未接受过化疗的健康人作为对照组。接下来是最关键的一步：单细胞基因组测序。研究人员从这些志愿者的血液或骨髓中，小心翼翼地分离出单个的HSPCs。然后，他们在培养皿中为这些孤独的细胞提供完美的生长环境，让每一个HSPC都分裂、增殖，形成一个由成千上万个细胞组成的“克隆集落 (colony)”。这个集落里的所有细胞，都拥有与最初那个HSPC完全相同的基因组（除了培养过程中可能产生的极少量新突变外）。这种“单细胞扩增”的策略，巧妙地解决了单个细胞DNA量太少而无法测序的难题。随后，研究人员对这些集落进行全基因组测序 (Whole-Genome Sequencing, WGS)，从而获得了每一个原始HSPC的完整基因图谱。通过比较同一个体不同HSPC之间的突变差异，他们得以构建出这些细胞的“家族树”，也就是系统发育树 (phylogenetic tree)。这棵树的树根代表着受精卵，树枝的每一次分叉都代表着一次新的突变事件，而树梢则代表着今天我们看到的这些HSPCs。树枝的长度，则精确地记录了突变的数量。通过这套方法，研究人员不仅能看到每个细胞里有多少突变，还能追溯这些突变是在生命中的哪个阶段、由什么原因造成的。一场针对化疗“罪证”的基因组级别的大侦探开始了。第一波冲击：化疗引发的“突变风暴”当测序结果呈现在眼前时，其震撼力是毋庸置疑的。研究人员发现，在23名化疗患者中，高达17人的HSPCs基因组中，出现了远超其年龄应有水平的突变数量。数据显示，有4位患者的情况最为严重，他们的HSPCs中，由化疗额外引入的突变数量超过了1000个。另外13位患者，也承受了中等程度的损伤，其HSPCs中额外增加了200到600个不等的突变。这意味着，他们的血细胞在短短的治疗周期内，经历了正常情况下需要几十年甚至更长时间才能完成的“衰老”过程。其中一个案例尤为令人心惊。一位年仅3岁的神经母细胞瘤患儿，在接受了包含卡铂 (carboplatin)和顺铂 (cisplatin)等药物的化疗后，其HSPCs中的体细胞突变总数，竟然已经超过了一位80岁健康老人的平均水平。换句话说，化疗让这个孩子的血细胞在基因组层面上，“一瞬间”衰老了近80年。这些冰冷的数字，无声地诉说着化疗药物在杀死癌细胞的同时，对正常组织造成的巨大附带伤害。然而，研究人员也注意到，并非所有化疗药物都是“冷血杀手”。有6位患者的突变水平与正常人无异，这暗示着化疗的遗传毒性存在着巨大的药物依赖性。这究竟是为什么？研究人员需要更精细的工具来“指认凶手”。化学指纹：锁定造成损伤的“元凶”不同的致突变物，会在DNA上留下独特的“犯罪痕迹”，这被称为突变印记 (mutational signature)。它就像一个人的指纹，具有高度的特异性。例如，阳光中的紫外线主要导致C>T的突变，且有其特定的序列偏好。通过分析基因组中成千上万个突变的模式，研究人员就能推断出导致这些突变的“元凶”。在这项研究中，研究人员从所有样本的基因组数据中，成功提取出了12种不同的单碱基替换（SBS）突变印记。其中4种是已知的、在正常人体内存在的印记，比如与衰老相关的SBS1和SBS5，以及一种血液细胞特有的印记SBSBlood。而真正激动人心的发现，是另外8种全新的、几乎只在化疗患者体内出现的突变印记。这些印记就是化疗药物留下的无可辩驳的“化学指纹”。通过将这些指纹与患者的用药史进行比对，研究人员成功地将它们与具体的药物一一对应起来：SBSA印记：主要特征是T>A的突变。它被发现于两位曾使用丙卡巴肼 (procarbazine)治疗霍奇金淋巴瘤的患者体内。丙卡巴肼是一种烷化剂，这个发现证实了它强大的致突变性。SBSC、SBSD、SBSE印记：这三种印记模式相似，都与一类被称为氮芥类 (nitrogen mustard)的烷化剂有关。SBSC的“指纹”指向了苯丁酸氮芥 (chlorambucil)；SBSD的“指纹”则指向了苯达莫司汀 (bendamustine)；而SBSE的“指纹”则与美法仑 (melphalan)的使用高度相关。SBSF印记：这个印记与铂类药物的暴露紧密相连，在接受过顺铂 (cisplatin)和卡铂 (carboplatin)治疗的患者中尤为明显。SBSG印记：它的“指纹”则清晰地指向了抗代谢药物5-氟尿嘧啶 (5-fluorouracil, 5-FU)及其口服前体药物卡培他滨 (capecitabine)。这些发现，就像是在一场复杂的犯罪现场，侦探通过分析弹道痕迹，准确地识别出了不同型号的凶器。它首次从基因组层面，为不同化疗药物的遗传毒性“画像”，并建立了直接的因果联系。同类不同命：为何“相似”的药物，毒性天差地别？这项研究最具有临床指导意义的发现之一，在于它揭示了即便是同一类别的化疗药物，其长期遗传毒性也可能存在天壤之别。以铂类药物为例，它们是治疗多种实体瘤的核心药物。研究发现，顺铂和卡铂会留下大量的SBSF突变印记，导致显著的基因组损伤。然而，同为铂类药物的奥沙利铂 (oxaliplatin)，即便在一些患者体内使用了长达22个周期，其造成的SBSF突变也微乎其微，几乎可以忽略不计。这一发现令人振奋。在许多临床场景中，这几种铂类药物在疗效上可以相互替代。这意味着，如果一位患者的治疗方案有选择空间，医生或许可以优先考虑使用奥沙利铂，从而在保证疗效的同时，极大地降低对正常血细胞的长期遗传损伤，减少未来发生继发性肿瘤的风险。类似的故事也发生在烷化剂中。美法仑、苯达莫司汀和苯丁酸氮芥都显示出强大的致突变能力。但另一位同类药物——环磷酰胺 (cyclophosphamide)，却表现得异常“温和”。在接受过环磷酰胺治疗的患者中，研究人员只观察到极少量的额外突变。这背后的原因可能是什么？研究人员推测，这与细胞的解毒能力有关。HSPCs细胞内含有一种高水平的酶，名为醛脱氢酶 (aldehyde dehydrogenase)，这种酶恰好能够高效地将环磷酰胺的活性代谢产物分解为无毒物质，从而保护了HSPCs免受其伤害。这些“同类不同命”的案例，为我们打开了一扇通往“精准化疗”或“低毒化疗”的大门。未来的化疗方案设计，或许不再仅仅是疗效和短期毒性的权衡，更可以基于基因组损伤的考量，做出更长远、更人性化的选择。不平等的战场：为何不同血细胞的“伤势”各不相同？化疗药物进入血液，会流经全身，但它们对不同类型血细胞的攻击，似乎也存在“偏好”。为了探究这一点，研究人员利用流式细胞分选技术 (flow sorting)，从患者血液中精确地分离出不同种类的成熟血细胞，包括单核细胞 (monocytes)、B淋巴细胞 (B cells)、记忆T淋巴细胞 (T memory cells)和初始T淋巴细胞 (T naive cells)，并对它们进行了深度测序。结果再次带来了惊喜。不同药物的“攻击偏好”差异巨大：5-氟尿嘧啶/卡培他滨 (SBSG印记)：这种药物对造血源头的HSPCs和单核细胞几乎“视而不见”，突变负担极低。然而，它却对淋巴细胞（B细胞和T细胞）痛下杀手，在这些细胞中造成了显著的突变累积。这可能是因为淋巴细胞的代谢途径或DNA修复机制，使它们对这种模拟胸腺嘧啶的药物尤为敏感。铂类药物 (SBSF印记)：情况恰好相反。铂类药物对HSPCs和单核细胞造成了最严重的打击，但在T细胞中造成的突变则相对较少。这种细胞类型的特异性损伤模式，揭示了一个更为复杂的画面。化疗的长期影响，不仅取决于药物本身，还取决于受攻击细胞的内在生物学特性，包括它们的代谢状态、DNA修复能力和细胞分裂速率。理解这些差异，将有助于我们更准确地预测和管理特定化疗方案可能带来的长期风险，例如针对免疫系统的损伤。时间的加速器：化疗如何让年轻的血液“未老先衰”除了直接增加突变数量，化疗还以另一种更隐蔽、也更深刻的方式，改变了我们的血液世界——它重塑了血细胞的克隆结构 (clonal architecture)，让整个系统出现了“未老先衰”的迹象。在正常衰老过程中，随着突变的自然累积，HSPCs中偶尔会出现一些携带“优势突变”的细胞。这些突变（例如在DNMT3A、TET2等基因上）赋予了细胞微弱的生长或生存优势，使其后代在HSPCs群体中逐渐占据主导地位，形成一个庞大的“克隆”。这种现象被称为意义不明确的克隆性造血 (Clonal Hematopoiesis of Indeterminate Potential, CHIP)，在70岁以上的老年人中非常普遍。一位健康的48岁个体，其HSPCs的“家族树”看起来枝繁叶茂、多样性极高，几乎看不到任何一个克隆占据绝对优势。而一位77岁的健康老人，其“家族树”则呈现出几支巨大的“主干”，这些就是由CHIP克隆扩张形成的。然而，当研究人员观察那些化疗患者的“家族树”时，他们看到了令人不安的景象。一位48岁的女性患者 (PD47703)，她在10岁时因霍奇金淋巴瘤接受过化疗，47岁时又因其他疾病再次化疗。她的HSPCs系统发育树，看起来完全不像一个中年人，反而更像是一位耄耋老人，充满了大大小小的扩张克隆。同样，一位43岁的女性患者 (PD37580)，在长期使用苯丁酸氮芥后，其血液的克隆结构也呈现出典型的“老年化”特征。更关键的是，化疗催生的这些“优势克隆”，与正常衰老产生的克隆，在驱动基因上存在本质不同。正常衰老催生的大多是携带DNMT3A或TET2突变的克隆，而化疗这片“焦土”上顽强生长起来的，则主要是那些携带DNA损伤应答 (DNA damage response)通路相关基因突变的克隆，尤其是PPM1D和TP53基因。这其中的逻辑不难理解。化疗通过制造大量的DNA损伤来杀死细胞。如果一个HSPC恰好发生了一个PPM1D或TP53的突变，这个突变可能会让细胞对DNA损伤“麻木”，从而在化疗的轮番轰炸中幸存下来。当其他“遵纪守法”的细胞大量死亡时，这些“作弊”的细胞就获得了巨大的生存空间，迅速扩张，主宰了整个造血系统。这种“过早衰老”的血液系统，潜藏着巨大的风险。一方面，这些携带PPM1D突变的克隆本身可能会削弱骨髓的再生能力。另一方面，TP53突变是众所周知的癌症驱动基因，它的扩张，大大增加了患者未来患上治疗相关的继发性白血病 (therapy-related leukemia)的风险。这恰恰解释了为什么部分癌症患者在多年后会罹患第二种、且往往更具侵袭性的血液肿瘤。化疗，在无意中为这些危险的细胞铺就了通往王座的道路。解读伤痕，是为了开创更安全的未来这项里程碑式的研究，为我们描绘了化疗对正常血细胞造成的长期、深刻且复杂的伤害。它告诉我们，化疗的代价，远不止于那些我们能看到或感受到的短期副作用。在基因组的层面上，它留下的伤痕可能会伴随患者的一生。然而，这项研究的目的绝不是为了制造恐慌，更不是要否定化疗在癌症治疗中的基石地位。恰恰相反，看清风险，是为了更好地规避风险。这些发现为我们指明了优化癌症治疗、保障患者长期健康的康庄大道。首先，它为优化化疗方案提供了全新的视角。当面临多种药物选择时，我们可以将“长期遗传毒性”作为一个重要的考量指标。选择像奥沙利铂或环磷酰胺这样“更温和”的药物，可能在不牺牲疗效的前提下，为患者赢得一个更健康的未来。其次，它为癌症患者的长期健康管理提供了强大的工具。通过在化疗后对患者的血液进行基因测序，医生可以评估其突变负担和克隆结构，识别出那些携带高风险突变（如TP53）的“危险克隆”。这使得主动监测和早期干预成为可能，从而将继发性肿瘤扼杀在摇篮里。最后，这项研究也向我们提出了一个更宏大的议题。随着医学的进步，癌症患者的数量日益增多。如何管理他们的长期健康，如何减轻治疗带来的“后遗症”，是整个社会和医学界面临的共同挑战。这项研究，正是应对这一挑战的坚实一步。参考文献Mitchell, E., Pham, M.H., Clay, A. et al. The long-term effects of chemotherapy on normal blood cells. Nat Genet (2025). https://doi.org/10.1038/s41588-025-02234-x声明：本文仅用于分享，不代表平台立场，如涉及版权等问题，请尽快联系我们，我们第一时间更正，谢谢！往期热文：Cell | “清空”细胞线粒体：顶尖研究创造出“僵尸干细胞”，揭示代谢如何掌控细胞命运Nature Aging | 逆转时光的魔术？解密RNA疗法如何改写衰老剧本Nature Genetics | 终结无模型之困：肠道类器官技术为研究人类特异性病原体开辟新纪元Nature Methods | 解密大脑“社交网络”：我们真的读懂了脑信号的“悄悄话”吗？Nature Genetics | 不再盲人摸象！革命性算法pgBoost整合多维信息，为GWAS变异找到真正的家Nature Medicine | 给肾脏“减负”，给血糖“泄洪”：SGLT2抑制剂破解1型糖尿病的“高滤过”与“高血糖”死循环

Active Ingredient Manufacturing Transfer to the U.S. Complete PRINCETON, N.J., July 1, 2025 /PRNewswire/ -- 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, announced today that it has successfully completed the transfer of the manufacturing process for its synthetic hypericin active ingredient under its partnership agreement with Sterling Pharma Solutions (Sterling). The transfer from Europe to the United States (U.S.) included the optimization and implementation of a commercially viable, scalable production process for this important active ingredient, which is used in the topical drug product formulations HyBryte™ and SGX302 being developed for the treatment of cutaneous T-cell lymphoma (CTCL) and psoriasis, respectively. Synthetic hypericin is a potent photosensitizer that is topically applied to skin lesions. Soligenix and Sterling have enabled cGMP (current good manufacturing practice) manufacturing for clinical trials with the intent of establishing a long-term commercial manufacturing collaboration. "We are pleased to have successfully produced larger quantities of cGMP synthetic hypericin, and look forward to continuing to work with Sterling to refine the process for process validation while further reducing our cost of goods," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "We look forward to building on our already strong relationship to advance our topical hypericin clinical programs, most notably, HyBryte™ for the treatment of early-stage CTCL, toward potential commercialization worldwide." "Sterling is pleased to be collaborating with Soligenix on this important program. We believe that Sterling's expertise in active pharmaceutical ingredient manufacturing, including developing innovative solutions such as continuous flow chemistry for this product, will continue to provide great value to the Soligenix program while we work towards a commercial supply agreement," stated Adam Kujath, Site Head at Sterling Pharma Solutions' Germantown, WI facility. 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 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 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 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. 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 FLASH 2, is expected to be initiated before the end of 2024. This study is a randomized, double-blind, placebo-controlled, multicenter study that will enroll approximately 80 subjects with early-stage CTCL. The FLASH 2 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 is being 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, see above), 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 data, with approximately 3,200 new cases seen annually) and approximately 38,000 individuals in Europe (based on ECIS prevalence estimates, with approximately 3,800 new cases annually). About Soligenix, Inc. Soligenix is a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need. Our Specialized BioTherapeutics business segment is developing and moving toward potential commercialization of HyBryte™ (SGX301 or synthetic hypericin sodium) as a novel photodynamic therapy utilizing safe visible light for the treatment of cutaneous T-cell lymphoma (CTCL). With successful completion of the second Phase 3 study, regulatory approvals will be sought to support potential commercialization worldwide. Development programs in this business segment also include expansion of synthetic hypericin (SGX302) into psoriasis, our first-in-class innate defense regulator (IDR) technology, dusquetide (SGX942) for the treatment of inflammatory diseases, including oral mucositis in head and neck cancer, and (SGX945) in Behçet's Disease. Our Public Health Solutions business segment includes development programs for RiVax®, our ricin toxin vaccine candidate, as well as our vaccine programs targeting filoviruses (such as Marburg and Ebola) and CiVax™, our vaccine candidate for the prevention of COVID-19 (caused by SARS-CoV-2). The development of our vaccine programs incorporates the use of our proprietary heat stabilization platform technology, known as ThermoVax®. To date, this business segment has been supported with government grant and contract funding from the National Institute of Allergy and Infectious Diseases (NIAID), the Defense Threat Reduction Agency (DTRA) and the Biomedical Advanced Research and Development Authority (BARDA). For further information regarding Soligenix, Inc., please visit the Company's website at and follow us on LinkedIn and Twitter at @Soligenix_Inc. This press release may contain forward-looking statements that reflect Soligenix's current expectations about its future results, performance, prospects and opportunities, including but not limited to, potential market sizes, patient populations, clinical trial enrollment, the expected timing for closing the offering described herein and the intended use of proceeds therefrom. Statements that are not historical facts, such as "anticipates," "estimates," "believes," "hopes," "intends," "plans," "expects," "goal," "may," "suggest," "will," "potential," or similar expressions, are forward-looking statements. These statements are subject to a number of risks, uncertainties and other factors that could cause actual events or results in future periods to differ materially from what is expressed in, or implied by, these statements, and include the expected amount and use of proceeds from the offering and the expected closing date of the offering. Soligenix cannot assure you that it will be able to successfully develop, achieve regulatory approval for or commercialize products based on its technologies, particularly in light of the significant uncertainty inherent in developing therapeutics and vaccines against bioterror threats, conducting preclinical and clinical trials of therapeutics and vaccines, obtaining regulatory approvals and manufacturing therapeutics and vaccines, that product development and commercialization efforts will not be reduced or discontinued due to difficulties or delays in clinical trials or due to lack of progress or positive results from research and development efforts, that it will be able to successfully obtain any further funding to support product development and commercialization efforts, including grants and awards, maintain its existing grants which are subject to performance requirements, enter into any biodefense procurement contracts with the U.S. Government or other countries, that it will be able to compete with larger and better financed competitors in the biotechnology industry, that changes in health care practice, third party reimbursement limitations and Federal and/or state health care reform initiatives will not negatively affect its business, or that the U.S. Congress may not pass any legislation that would provide additional funding for the Project BioShield program. In addition, there can be no assurance as to the timing or success of any of its clinical/preclinical trials. Despite the statistically significant result achieved in the first HyBryte™ (SGX301) Phase 3 clinical trial for the treatment of cutaneous T-cell lymphoma or any other studies (including the open-label, investigator-initiated study), there can be no assurance that the second HyBryte™ (SGX301) Phase 3 clinical trial will be successful or that a marketing authorization from the FDA or EMA will be granted. Additionally, although the EMA has agreed to the key design components of the second HyBryte™ (SGX301) Phase 3 clinical trial, no assurance can be given that the Company will be able to modify the development path to adequately address the FDA's concerns or that the FDA will not require a longer duration comparative study. Notwithstanding the result in the first HyBryte™ (SGX301) Phase 3 clinical trial for the treatment of cutaneous T-cell lymphoma and the Phase 2a clinical trial of SGX302 for the treatment of psoriasis, there can be no assurance as to the timing or success of the clinical trials of SGX302 for the treatment of psoriasis. Additionally, despite the biologic activity observed in aphthous ulcers induced by chemotherapy and radiation, there can be no assurance as to the timing or success of the clinical trials of SGX945 for the treatment of Behçet's Disease. Further, there can be no assurance that RiVax® will qualify for a biodefense Priority Review Voucher (PRV) or that the prior sales of PRVs will be indicative of any potential sales price for a PRV for RiVax®. Also, no assurance can be provided that the Company will receive or continue to receive non-dilutive government funding from grants and contracts that have been or may be awarded or for which the Company will apply in the future. These and other risk factors are described from time to time in filings with the Securities and Exchange Commission (the "SEC"), including, but not limited to, Soligenix's reports on Forms 10-Q and 10-K. Unless required by law, Soligenix assumes no obligation to update or revise any forward-looking statements as a result of new information or future events. SOURCE SOLIGENIX, INC. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED