Treatment with Auxora™ shown to potentially reduce the severity of asparaginase-associated pancreatitis, also called asparaginase-induced pancreatic toxicity, in pediatric patients with acute lymphoblastic leukemia

Auxora治疗™在患有急性淋巴细胞白血病的儿科患者中，显示出可能降低天冬酰胺酶相关胰腺炎（也称为天冬酰胺酶诱导的胰腺毒性）的严重程度

Auxora eliminated the need for total parenteral nutrition and resulted in a 53% reduction in days in hospital and a 40% reduction in intensive care unit days as compared to historical matched control group

与历史匹配的对照组相比，Auxora消除了对全胃肠外营养的需求，住院天数减少了53%，重症监护病房天数减少了40%

None of the Auxora-treated patients had significant necrosis compared to 27% of historical control patients at 30 days

与30天时历史对照组患者的27%相比，接受Auxora治疗的患者均未出现明显坏死

LA JOLLA, Calif., Dec. 11, 2023 /PRNewswire/ -- CalciMedica Inc. (CalciMedica) (Nasdaq: CALC), a clinical-stage biopharmaceutical company focused on developing novel calcium release-activated calcium (CRAC) channel inhibition therapies for acute and chronic inflammatory and immunologic diseases, today announced that its collaborator, St.

加利福尼亚州拉霍亚，2023年12月11日/PRNewswire/--CalciMedica Inc.（CalciMedica）（纳斯达克：CALC），一家临床阶段的生物制药公司，专注于开发用于急性和慢性炎症和免疫疾病的新型钙释放激活钙（CRAC）通道抑制疗法，今天宣布其合作者St。

Jude Children's Research Hospital (SJCRH), presented data from the initial cohort of the Phase 1/2 CRSPA study of Auxora™ (zegocractin injectable emulsion) in asparaginase-induced pancreatic toxicity (AIPT) at the 65th Annual American Society of Hematology (ASH) Meeting & Exposition on Sunday, December 10, 2023, in San Diego, CA..

裘德儿童研究医院（SJCRH）提供了来自Auxora 1/2期CRSPA研究初始队列的数据™2023年12月10日（星期日）在加利福尼亚州圣地亚哥举行的第65届美国血液学会（ASH）年会和博览会上，天冬酰胺酶诱导的胰腺毒性（AIPT）中的（zegocractin可注射乳剂）。。

'It is extremely encouraging to see the results of our CRSPA study in this first cohort of patients as we continue to enroll new patients and expand to additional sites,' said Sudarshan Hebbar, M.D., Chief Medical Officer of CalciMedica. 'Notably, treatment with Auxora delivered positive results across multiple clinical endpoints.

CalciMedica首席医疗官Sudarshan Hebbar医学博士说：“随着我们继续招募新患者并扩大到其他地点，在第一批患者中看到我们的CRSPA研究结果非常令人鼓舞。”值得注意的是，Auxora治疗在多个临床终点都取得了积极的结果。

The elimination of the need for total parenteral nutrition, or TPN, for CRSPA patients who were able to eat on their own is particularly encouraging given that over half of the patients in the historical control group required TPN for several weeks on average. The ability to tolerate solid food correlates with pancreatic health and recovery from pancreatitis.

考虑到历史对照组中超过一半的患者平均需要TPN数周，消除了能够自己进食的CRSPA患者对全胃肠外营养（TPN）的需求尤其令人鼓舞。耐受固体食物的能力与胰腺健康和胰腺炎的恢复有关。

Importantly, we saw an improvement in solid food tolerance in our Phase 2a acute pancreatitis trial, and time to solid food tolerance is the primary endpoint of our CARPO trial in adult patients with acute pancreatitis, which we expect to read out in the first half of 2024. With no approved therapies for asparaginase-induced pancreatic toxicity or acute pancreatitis on the market, we are excited about the potential benefits that Auxora could provide patients.'.

重要的是，我们在2a期急性胰腺炎试验中看到固体食物耐受性有所改善，固体食物耐受时间是我们对成人急性胰腺炎患者进行CARPO试验的主要终点，我们预计将在2024年上半年宣读。由于市场上没有批准用于天冬酰胺酶诱导的胰腺毒性或急性胰腺炎的疗法，我们对Auxora可能为患者提供的潜在益处感到兴奋。”。

Investigators at SJCRH presented results from the first cohort of the CRSPA study, consisting of nine children (average age 8.2 years) with acute lymphoblastic leukemia (ALL) experiencing asparaginase-associated pancreatitis, also known as AIPT and referred to as AAP in the abstract. AIPT is a severe complication that can arise during the treatment of ALL patients, the majority of which are children, characterized by intense abdominal pain, nausea, vomiting and systemic inflammatory response syndrome (SIRS).

SJCRH的研究人员介绍了CRSPA研究的第一个队列的结果，该研究由9名患有天冬酰胺酶相关性胰腺炎（也称为AIPT）的急性淋巴细胞白血病（ALL）儿童（平均年龄8.2岁）组成，在摘要中称为AAP。AIPT是所有患者（其中大多数是儿童）治疗过程中可能出现的严重并发症，其特征是剧烈腹痛，恶心，呕吐和全身炎症反应综合征（SIRS）。

AIPT can lead to further chronic problems such as insulin dependence, exocrine pancreatic insufficiency and chronic pain. Many of these children can no longer be treated with current asparaginase therapy (e.g., ONCASPAR™ and RYLAYZE™) which can have a negative impact on their recovery from ALL.  Eight of nine patients in the CRSPA study received a full regimen of 4 daily doses of Auxora at dose level 1 (30mg/m2 on day 1 and 42mg/m2 on days 2-4) administered as a four-hour infusion.

AIPT可导致进一步的慢性问题，例如胰岛素依赖，胰腺外分泌功能不全和慢性疼痛。这些儿童中的许多人不再能接受目前的天冬酰胺酶治疗（例如，ONCASPAR™和RYLAYZE™)这可能会对他们从所有人中恢复产生负面影响。CRSPA研究中的9名患者中有8名接受了剂量水平为1（第1天为30mg/m2，第2-4天为42mg/m2）的4日剂量Auxora的完整方案，作为4小时输注给药。

Results from these patients were compared to a historical matched control group of 16 patients with imaging results out of a total of 51 patients who developed AIPT within 30 days of receiving asparaginase in the Total Therapy XVI study (T16)..

在total Therapy XVI研究（T16）中，51名患者在接受天冬酰胺酶治疗后30天内发生AIPT，将这些患者的结果与16名患者的历史匹配对照组进行了比较。。

Treatment with Auxora, as compared to the historical matched control group, was shown to have the potential to reduce the severity of AIPT in pediatric patients with ALL. Study results showed that Auxora reduced the average number of days patients spent in the hospital from 13.4 to 6.3 days. The need for intensive care unit (ICU) care was also reduced, with three control patients (18.8%) requiring ICU care compared to one treated patient (12.5%), and the average number of days in the ICU was reduced from 5 to 3 days.

与历史匹配的对照组相比，Auxora治疗有可能降低ALL患儿AIPT的严重程度。研究结果表明，Auxora将患者住院的平均天数从13.4天减少到6.3天。重症监护病房（ICU）护理的需求也减少了，与一名接受治疗的患者（12.5%）相比，三名对照患者（18.8%）需要ICU护理，ICU的平均天数从5天减少到3天。

Additionally, no patients in the CRSPA study required TPN, compared to 68.8% in the historical matched control group, who required 27 days of nutritional support on average. Finally, blinded central reading of pancreatic imaging showed a reduction in the development of significant pancreatic necrosis (≥30%) and the severity of acute pancreatitis by CT severity index (CTSI) scoring in patients treated with Auxora compared to the historical matched cohort.

此外，CRSPA研究中没有患者需要TPN，而历史匹配对照组为68.8%，平均需要27天的营养支持。最后，胰腺成像的盲法中央读数显示，与历史匹配队列相比，接受Auxora治疗的患者的CT严重程度指数（CTSI）评分降低了显着胰腺坏死（≥30%）的发展和急性胰腺炎的严重程度。

Based on these results, investigators have established dose level 1 as the recommended Phase 2 dose (RP2D) of Auxora for children with ALL experiencing AIPT..

基于这些结果，研究人员将剂量水平1确定为ALL经历AIPT的儿童Auxora的推荐2期剂量（RP2D）。。

Total 16 (T16): All AIPT

总计16（T16）：所有AIPT

Matched T16 AIPT cohort

匹配的T16 AIPT队列

CRSPA evaluable for efficacy

CRSPA可评估疗效

Patients with AIPT

AIPT患者

51

51

16

16

8

8

Age: mean (range)

年龄：平均（范围）

10.3 (2.2-19.4)

10.3 (2.2-19.4)

9 (2.2-18.4)

9 (2.2-18.4)

8.2 (3.1-17.6)

8.2 (3.1-17.6)

Female (%)

女性（%）

17 (33.3 %)

17 (33.3 %)

5 (31.3 %)

5 (31.3 %)

3 (37.5 %)

3 (37.5 %)

Low-risk therapy (%)

低风险治疗（%）

9 (17.6 %)

9 (17.6 %)

1 (6.3 %)

1 (6.3 %)

2 (25 %)

Hospital days (range)

住院天数（范围）

12.1 (2-70)

12.1 (2-70)

13.4 (2-27)

13.4 (2-27)

6.3 (5-8)

6.3 (5-8)

ICU needed (%)

需要ICU（%）

11 (21.6 %)

11 (21.6 %)

3 (18.8 %)

3 (18.8 %)

1 (12.5 %)

1 (12.5 %)

ICU days mean (range)

ICU平均天数（范围）

5.1 (1-9)

5.1 (1-9)

5 (3-7)

5 (3-7)

3

3

TPN needed (%)

需要TPN（%）

27 (52.9 %)

27 (52.9 %)

11 (68.8 %)

11 (68.8 %)

0

0

TPN days mean (range)

TPN天数平均值（范围）

37.7 (3-153)

37.7 (3-153)

27.2 (4-63)

27.2 (4-63)

NA

≥30% pancreatic necrosis (%)

≥30%胰腺坏死（%）

NA

不适用

4 (26.7%) *

4 (26.7%) *

0

0

CTSI mean (range)

CTSI平均值（范围）

NA

不适用

5.4 (0-10) *

5.4 (0-10) *

2.4 (0-4)

2.4 (0-4)

CTSI ≥ 7 (%)

CTSI≥7（%）

NA

不适用

4 (26.7%) *

4 (26.7%) *

0

0

*One patient in matched T16 cohort was unable to be evaluated for pancreatic necrosis or a CTSI score

*匹配的T16队列中的一名患者无法评估胰腺坏死或CTSI评分

CTSI score definitions:0-3 mild acute pancreatitis4-6 moderately severe acute pancreatitis≥7 severe acute pancreatitis

CTSI评分定义：0-3轻度急性胰腺炎4-6中度重症急性胰腺炎≥7重症急性胰腺炎

About AIPT and CRSPAAIPT is an ultra-orphan indication affecting 300-400 pediatric patients in the US each year. Asparaginase (e.g. ONCASPAR™ and RYLAYZE™), an enzyme that degrades the amino acid asparagine, which is essential for the leukemic cells to survive, is one of the mainstays of therapy in pediatric ALL patients.

关于AIPT和CRSPAAIPT是一种超孤儿适应症，每年影响美国300-400名儿科患者。天冬酰胺酶（例如ONCASPAR™和RYLAYZE™),一种降解氨基酸天冬酰胺的酶是儿科ALL患者治疗的主要手段之一，天冬酰胺是白血病细胞存活所必需的。

However, the administration of asparaginase triggers the development of AAP or AIPT in 7-10% of patients, including the over 4,000 pediatric ALL patients treated per year in the United States, with similar numbers in Europe. The first cohort in the dose-finding part of the CRSPA study consisting of 9 patients has been completed at SJCRH and investigators believe that an optimal pediatric dose for Auxora™ in this setting has been defined.

然而，天冬酰胺酶的使用会引发7-10%的患者发生AAP或AIPT，其中包括美国每年接受治疗的4000多名儿科ALL患者，欧洲的人数相似。由9名患者组成的CRSPA研究剂量发现部分的第一个队列已经在SJCRH完成，研究人员认为Auxora的最佳儿科剂量™在此设置中已定义。

The study has continued to enroll patients beyond the initial 9 patient cohort and is being expanded to additional sites. The full study plans for 24 patients at the optimal dose. Details of the CRSPA study are available on clinicaltrials.gov (NCT04195347)..

该研究继续招募最初9名患者队列以外的患者，并正在扩展到其他地点。完整的研究计划以最佳剂量为24名患者。CRSPA研究的详细信息可在clinicaltrials.gov（NCT04195347）上找到。。

About CARPOCARPO is an international, randomized, double-blind, placebo-controlled, dose-ranging trial intended to establish efficacy in AP with accompanying SIRS. It is expected to enroll 216 patients. AP can be a life-threatening condition where the pancreas becomes inflamed, sometimes leading to pancreatic cell death or necrosis, systemic inflammation, organ failure and death.

关于CARPOCARPO是一项国际性，随机，双盲，安慰剂对照，剂量范围的试验，旨在确定伴随SIRS的AP疗效。预计将招募216名患者。AP可能是一种危及生命的疾病，胰腺发炎，有时会导致胰腺细胞死亡或坏死，全身炎症，器官衰竭和死亡。

There are an estimated 275,000 hospitalizations for AP annually in the United States, of which approximately 40% present with SIRS, which can compromise the function of other tissues or organs, especially the lungs. Organ failure is responsible for much of the mortality seen in AP. There is currently no approved therapy for AP.

据估计，美国每年有275000例AP住院治疗，其中约40%患有SIRS，这可能会损害其他组织或器官的功能，尤其是肺部。器官衰竭是造成AP死亡率的主要原因。目前还没有批准的AP治疗方法。

Details of the CARPO trial are available on clinicaltrials.gov (NCT04681066)..

有关CARPO试验的详细信息，请访问clinicaltrials.gov（NCT04681066）。。

About CalciMedicaCalciMedica is a clinical-stage biopharmaceutical company focused on developing novel CRAC channel inhibition therapies for inflammatory and immunologic diseases. CalciMedica's proprietary technology targets the inhibition of CRAC channels to modulate the immune response and protect against tissue cell injury, with the potential to provide therapeutic benefits in life-threatening inflammatory and immunologic diseases for which there are currently no approved therapies.

关于Calcimedica Calcimedica是一家临床阶段的生物制药公司，专注于开发针对炎症和免疫疾病的新型CRAC通道抑制疗法。CalciMedica的专有技术旨在抑制CRAC通道以调节免疫反应并防止组织细胞损伤，有可能为目前尚无批准疗法的威胁生命的炎症和免疫疾病提供治疗益处。

CalciMedica's lead product candidate Auxora™, a proprietary, intravenous-formulated CRAC channel inhibitor, has demonstrated positive and consistent clinical results in multiple completed efficacy clinical trials. CalciMedica is currently conducting a Phase 2b trial for a planned 216 patients (called CARPO – NCT04681066) for AP with SIRS, with topline data expected in the first half of 2024, as well as continuing the Phase 1/2 CRSPA AIPT study, with additional data expected by the second half of 2024.

CalciMedica的主要候选产品Auxora™,一种专有的静脉内配制的CRAC通道抑制剂在多项已完成的疗效临床试验中显示出积极且一致的临床结果。CalciMedica目前正在为计划中的216名患有SIRS的AP患者（称为CARPO–NCT04681066）进行2b期试验，预计2024年上半年将有topline数据，并继续进行1/2期CRSPA AIPT研究，预计2024年下半年将有更多数据。

A Phase 2 study in acute kidney injury (AKI) is planned for early 2024. CalciMedica was founded by scientists from Torrey Pines Therapeutics and the Harvard CBR Institute for Biomedical Research, and is headquartered in La Jolla, CA. For more information, please visit www.calcimedica.com..

计划于2024年初进行急性肾损伤（AKI）的2期研究。CalciMedica由Torrey Pines Therapeutics和哈佛CBR生物医学研究所的科学家创立，总部位于加利福尼亚州拉霍亚。有关更多信息，请访问www.CalciMedica.com。。

Forward-Looking StatementsThis communication contains forward-looking statements which include, but are not limited to, statements regarding CalciMedica's preliminary analysis, assessment and conclusions of the results of the first cohort of the Phase 1/2 CRSPA study; the design and potential benefits of Auxora, including its potential to reduce the severity of AIPT in pediatric patients with ALL; CalciMedica's plans and expected timing for developing its product candidates and potential benefits of its product candidates; CalciMedica's ongoing and planned clinical trials; the timing of the planned initiation of a Phase 2 study in AKI; the development and outcomes of CARPO and CRSPA trial programs, including the milestones, data announcements, expected enrollment, site expansion, potential benefits of and any other potential results related thereto; and the belief that an optimal pediatric dose for Auxora for children with ALL experiencing AIPT has been defined.

前瞻性声明本通讯包含前瞻性声明，其中包括但不限于CalciMedica对1/2期CRSPA研究第一组结果的初步分析，评估和结论的声明；Auxora的设计和潜在益处，包括其降低小儿ALL患者AIPT严重程度的潜力；CalciMedica开发候选产品的计划和预期时间以及候选产品的潜在利益；CalciMedica正在进行和计划进行的临床试验；计划在AKI开始第二阶段研究的时间；CARPO和CRSPA试验计划的发展和结果，包括里程碑，数据公告，预期入学率，网站扩展，潜在收益以及与之相关的任何其他潜在结果；并且已经确定了ALL经历AIPT的儿童Auxora的最佳儿科剂量。

These forward-looking statements are subject to the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. CalciMedica's expectations and beliefs regarding these matters may not materialize. Actual outcomes and results may differ materially from those contemplated by these forward-looking statements as a result of uncertainties, risks, and changes in circumstances, including but not limited to risks and uncertainties related to: the impact of fluctuations in global financial markets on CalciMedica's business and the actions it may take in response thereto; CalciMedica's ability to execute its plans and strategies; the ability to obtain and maintain regulatory approval for Auxora; results from clinical trials may not be indicative of results that may be observed in the future; potentia.

这些前瞻性声明受1995年《私人证券诉讼改革法案》中安全港条款的约束。CalciMedica对这些问题的期望和信念可能不会实现。由于不确定性、风险和环境变化，实际结果和结果可能与这些前瞻性声明所预期的结果和结果存在重大差异，包括但不限于与以下相关的风险和不确定性：全球金融市场波动对CalciMedica业务的影响及其可能采取的应对措施；CalciMedica执行其计划和战略的能力；获得和维持Auxora监管批准的能力；临床试验的结果可能无法表明未来可能观察到的结果；潜力。

CalciMedica Contact:

CalciMedica联系人：

Investors and MediaArgot Partners Sarah Sutton/Kevin Murphy[email protected](212) 600-1902

投资者和MediaArgot合作伙伴Sarah Sutton/Kevin Murphy[受电子邮件保护]（212）600-1902

SOURCE CalciMedica, Inc.

来源CalciMedica，Inc。