ORAI1

Last patient enrolled in CARPO, Phase 2b trial of Auxora™ in acute pancreatitis (AP); topline data expected in 2Q 2024 KOURAGE, Phase 2 trial in severe acute kidney injury (AKI) remains on track to initiate patient enrollment in 2Q 2024 with data expected in 2025 Collaborators from Cedars-Sinai to present abstract on human proteomics data supporting the potential benefits of Auxora in AP at Digestive Disease Week (DDW) 2024 Cash position expected to fund operations into 2H 2025 LA JOLLA, Calif., May 13, 2024 /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 illnesses, today reported financial results for the first quarter ended March 31, 2024. "This past quarter was transformational for CalciMedica. We completed enrollment in our Phase 2b CARPO trial in AP, we received FDA clearance on our IND application and started work on KOURAGE, our Phase 2 trial in patients with severe AKI, and we continued to progress our other programs, with multiple value-creating milestones on the horizon," said Rachel Leheny, Ph.D., Chief Executive Officer of CalciMedica. "Our progress was further supported by a private placement of up to approximately $54 million including an upfront investment of $20.4 million and a potential additional approximately $33.1 million from accompanying warrants that trigger upon announcement of clinical trial data. We expect our cash, cash equivalents and short-term investments will provide funding into the second half of 2025. We look forward to continuing to advance our programs and to announcing topline data from CARPO later this quarter." Recent Clinical and Preclinical Updates and Anticipated Milestones: Last patient enrolled in Phase 2b CARPO trial and topline data expected in 2Q24: In April 2024, CalciMedica enrolled the last patient in CARPO, the Company's randomized, double-blind, placebo-controlled Phase 2b trial of Auxora™ in acute pancreatitis (AP) patients, reaching full target enrollment of 216 patients. Topline data from the trial is expected to be announced later this quarter. Phase 2 KOURAGE trial initiation underway: In February 2024, CalciMedica received clearance of its Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA) for Auxora to be evaluated in a Phase 2 trial in severe acute kidney injury (AKI) with associated acute hypoxemic respiratory failure (AHRF), which has been named KOURAGE. CalciMedica expects to enroll the first patient in KOURAGE later this quarter, with data expected in 2025. Abstract accepted for poster presentation at DDW 2024: CalciMedica collaborator Richard Waldon, Ph.D., of Cedars-Sinai Medical Center will be presenting a poster titled "Serum Proteomics Reveals That the Orai1 Inhibitor Auxora May Provide Benefits in Severe Acute Pancreatitis Similar to Those Seen in COVID-19 Pneumonia" at the upcoming DDW 2024 meeting on Saturday, May 18th from 12:30-1:30 p.m. ET. Preclinical data presented at AKI & CRRT: In March 2024, CalciMedica collaborator David Basile, Ph.D., of Indiana University presented data from preclinical studies of Auxora in AKI at the 29th International Acute Kidney Injury and Continuous Renal Replacement Therapy Conference (AKI & CRRT) in San Diego, CA. The results of the studies indicate that Auxora has the ability to hasten the recovery of kidney function and improve survival in rat models of AKI through inhibiting the Orai1 channels on Th17 and endothelial cells. CRSPA study expanded and continuing to enroll in Phase 2 portion of trial: The CRSPA study in asparaginase-induced pancreatic toxicity (AIPT) has been expanded to additional sites, and the dose used in the initial cohort has been established as the recommended Phase 2 dose and a target total trial enrollment has been set at 24. Data is expected in 2025. Financial Results for the Three Months Ended March 31, 2024: In January 2024, CalciMedica completed a private placement of securities to new and existing investors for up to approximately $54 million in gross proceeds that includes initial upfront funding of $20.4 million and up to an additional approximately $33.1 million upon exercise of accompanying warrants. The upfront net proceeds from the private placement will support the Company's ongoing Phase 2 CARPO trial for Auxora in AP and planned Phase 2 KOURAGE trial for Auxora in AKI. As of March 31, 2024, CalciMedica had approximately $25.7 million in cash, cash equivalents and short-term investments, which, based on its current operating plan, CalciMedica expects to be sufficient to fund its operations into the second half of 2025. Total loss from operations for the three months ended March 31, 2024, was approximately $5.8 million, which was offset by a gain from the fair value adjustment to the warrant liability of $5.6 million and interest income of $0.3 million. With the impact of a $5.6 million non-cash gain from the fair value adjustment of the warrant liability, net income was $0.1 million, or $0.01 per share (basic and diluted) for the three months March 31, 2024. About CalciMedica CalciMedica 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. 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 (called CARPO – NCT04681066) for AP with SIRS, with topline data expected in the second quarter of 2024, as well as supporting the ongoing Phase 1/2 AIPT study (called CRSPA – NCT04195347), with data expected in 2025. CalciMedica plans to initiate patient enrollment its Phase 2 study (called KOURAGE – NCT06374797) in AKI with associated AHRF in the second quarter of 2024 with data expected in 2025. 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 . Forward-Looking Statements This communication contains forward-looking statements which include, but are not limited to, CalciMedica's expected use of proceeds from the private placement; any additional gross proceeds that may be received by CalciMedica upon exercise, if any, of the accompanying warrants issued in the private placement; CalciMedica's expected cash runway; CalciMedica's business strategy; the potential for multiple value-creating milestones on the horizon; CalciMedica's planned and ongoing clinical trials and the timing, design, expected patient enrollment thereof and the expected timing for the release of data from those trials, including its Phase 2b CARPO trial of Auxora for AP with accompanying SIRS, its ongoing Phase ½ CRSPA trial of Auxora in pediatric patients with AIPT and its planned Phase 2 KOURAGE trial of Auxora in AKI with associated AHRF; the potential benefits of Auxora for the treatment of AP, AIPT and AKI; and the potential of CalciMedica's proprietary technology to provide therapeutic benefits in life-threatening inflammatory and immunologic diseases. 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 or preclinical studies may not be indicative of results that may be observed in the future; potential safety and other complications from Auxora; the scope, progress and expansion of developing and commercializing Auxora; the size and growth of the market therefor and the rate and degree of market acceptance thereof; economic, business, competitive, and/or regulatory factors affecting the business of CalciMedica generally; CalciMedica's ability to protect its intellectual property position; and the impact of government laws and regulations. Additional risks and uncertainties that could cause actual outcomes and results to differ materially from those contemplated by the forward-looking statements are included under the caption "Risk Factors" in CalciMedica's Annual Report on Form 10-Q for the quarter ended March 31, 2024, being filed with the Securities and Exchange Commission (SEC) later today, and elsewhere in CalciMedica's subsequent reports on Form 10-K, Form 10-Q or Form 8-K filed with the SEC from time to time and available at . These documents can be accessed on CalciMedica's web page at ir.calcimedica.com/financials-filings/sec-filings. The forward-looking statements contained herein are made as of the date hereof, and CalciMedica undertakes no obligation to update them after this date, except as required by law. CalciMedica Contact: Investors and Media Argot Partners Sarah Sutton/Kevin Murphy [email protected] (212) 600-1902 SOURCE CalciMedica, Inc.

Therapeutic treatment with Auxora shown to hasten the recovery of kidney function and improve survival in a rat model of acute kidney injury (AKI) Preclinical results are consistent with clinical observations made with Auxora, supporting the KOURAGE trial in patients with severe AKI that will start enrolling in 2Q 2024 LA JOLLA, Calif., March 13, 2024 /PRNewswire/ -- CalciMedica Inc. (CalciMedica or the Company) (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, last evening presented data from preclinical studies of Auxora™ in acute kidney injury (AKI) at the 29th International Acute Kidney Injury and Continuous Renal Replacement Therapy Conference (AKI & CRRT) in San Diego, CA. David Basile, Ph.D., Professor of Anatomy, Cell Biology and Physiology at Indiana University, gave an oral and poster presentation entitled "The Store-Operated Calcium Channel Inhibitor Auxora Improves Renal Function Following Ischemia-Induced Acute Kidney Injury in Rats." "At AKI & CRRT, Prof. Basile discussed the most recent preclinical study of Auxora in an acute kidney injury model that used a treatment regimen of three daily doses of drug started six hours after ischemic injury, which resembles the dosing in our clinical protocol. The positive results from this study build on prior preclinical data and indicate that inhibiting Orai1 activity in an AKI model improves kidney function," said Kenneth Stauderman, Ph.D., Founder and Chief Scientific Officer of CalciMedica. "In rats with ischemic kidney injury akin to Stage 2 AKI, Auxora was shown to provide nearly complete recovery of kidney function, as evidenced by improved glomerular filtration rate (GFR) at 72 hours after injury, while placebo-treated animals showed little improvement in GFR. In rats with kidney injury akin to Stage 3 AKI, the rats treated with placebo died while those on Auxora survived and showed modest recovery of GFR. We are excited as these studies support clinical observations of Auxora that suggest the drug may be beneficial for AKI patients." AKI is a serious acute critical illness and denotes a sudden reduction in kidney function, or the organ's ability to clean and filter the blood, that results from a complication of critical illness. These animal model studies support observations from CalciMedica's clinical trials, particularly CARDEA, the Company's Phase 2 trial in patients with severe and critical COVID-19 pneumonia, where AKI was a relatively common co-morbidity or a common sequela of the disease. Compared to placebo-treated patients, Auxora-treated patients in CARDEA had lower levels of key biomarkers associated with kidney injury, lower incidence of treatment-emergent AKI and reduced mortality in those patients with decreased kidney function at the time of treatment. Additionally, previous preclinical studies conducted by CalciMedica and others suggest that Orai1 activity contributes to the activation and infiltration of pro-inflammatory Th17 cells in the kidney, which is associated with the development of AKI. CalciMedica has also shown that the active ingredient in Auxora, zegocractin, inhibits release of IL-17, which is a key pro-inflammatory cytokine from Th17 cells. "As we initiate KOURAGE, our Phase 2 trial of Auxora in severe AKI patients with associated acute hypoxemic respiratory failure, we are encouraged to have additional supporting data showing that Auxora has beneficial activity in animal models of AKI," said Sudarshan Hebbar, M.D., Chief Medical Officer of CalciMedica. "Patients randomized in KOURAGE will have Stage 2 and Stage 3 AKI, so the results from Prof. Basile's recent preclinical study, most notably the survival benefit, are particularly meaningful. Severe AKI in the presence of respiratory failure has a mortality of approximately 50% and we are heartened to see that Auxora has the potential for a positive impact on patients with this devastating disease." Data Presented at the AKI & CRRT Conference The data presented at AKI & CRRT was from a series of studies referred to as Study 1 and Study 2. In Study 1, AKI was induced in a rat model through ischemia reperfusion injury (I/R), a transient ligation of the renal artery, while control animals underwent sham-surgery. Within 30 minutes of injury, the animals were treated with a single intravenous infusion of either 16 mg/kg of Auxora or placebo over a period of 4 hours. GFR, an important indicator of kidney function, was evaluated at 24 hours post-injury. Study 2 evaluated recovery of kidney function following I/R similar to Study 1 but varying in intensity to mimic different severity of disease. In Study 2, GFR was measured 2-4 hours after injury but before treatment, and treatment with 16 mg/kg of Auxora or placebo was administered at 6, 24 and 48 hours post-injury, with GFR again evaluated at 72 hours. Results from Study 1 showed that at 24 hours post-injury, GFR was significantly higher in rats treated with Auxora 30 minutes after injury versus placebo (61%, p<0.05). Additionally, animals treated with Auxora showed a reduction in Th17 cells in the kidney of approximately 50% as compared to those treated with placebo. In Study 2, in a group of animals with initial GFR reductions of approximately 50%, similar to Stage 2 AKI, GFR at 72 hours was significantly greater in Auxora-treated animals as compared to placebo-treated animals (0.81±0.03 vs. 0.47±0.04 ml/min/100g respectively; p<0.001). In a group of animals with GFR reductions ≥66%, similar to Stage 3 AKI, placebo-treated rats experienced 100% mortality by 72 hours while Auxora-treated rats had no mortality at 72 hours and were stable, showing modest recovery of kidney function. These results indicate that Auxora has the ability to hasten the recovery of kidney function and improve survival in rat models of AKI. About AKI Acute kidney injury (AKI) denotes a sudden reduction in kidney function, or the organ's ability to clean and filter the blood, as measured by increased serum creatinine (a cellular waste product) or decreased urine volume. AKI can result as a complication of critical illness such as sepsis, pneumonia and acute pancreatitis, and other causes such as trauma, surgery and burns. There are approximately 3.7 million patients hospitalized with AKI in the United States each year. The majority have Stage 1 AKI and recover with supportive care alone. However, approximately 1.1 million of these patients advance to Stage 2 and Stage 3 AKI, over half of whom have associated acute hypoxemic respiratory failure (AHRF). The risk of serious morbidities and mortality is significant for advanced Stage 2 and Stage 3 AKI patients. There are currently no approved therapies for AKI. About KOURAGE KOURAGE is a randomized, double-blind, placebo-controlled study that will evaluate 150 patients with Stage 2 and 3 AKI who have AHRF and are receiving oxygen by non-invasive mechanical ventilation, high flow nasal cannula or intermittent mandatory ventilation (IMV). Patients will be stratified by classification of stage of AKI as well as the use of IMV. Patients will receive either a four-hour infusion of Auxora or placebo at 1.25 mL/kg as a first dose, after which they will receive Auxora or placebo at 1.0 mL/kg at hours 24, 48, 72 and 96. The primary endpoint of the trial will be evaluation of patients through day 30 to determine days alive, ventilator-free and dialysis-free. Secondary endpoints will include a composite of: all-cause mortality, decrease in estimated glomerular filtration rate (eGFR), and the incidence of dialysis over a period of 90 days, also known as MAKE-90 (Major Adverse Kidney Events at 90 days). About Auxora™ CalciMedica's lead clinical compound, Auxora™, is a potent and selective small molecule inhibitor of Orai1-containing CRAC channels that is being developed for use in patients with acute inflammatory and immunologic illnesses. CRAC channels are found on many cell types, including immune system cells, endothelium cells and pancreatic acinar cells, where aberrant activation of these channels may play a key role in the pathobiology of acute and chronic inflammatory syndromes. Auxora is currently being evaluated in: (i) a Phase 2b trial for acute pancreatitis (AP) with accompanying systemic inflammatory response syndrome (SIRS), called CARPO, (ii) an investigator-sponsored Phase 1/2 trial, called CRSPA, being conducted in pediatric patients with asparaginase-induced pancreatic toxicity (AIPT) as a side effect of pediatric acute lymphoblastic leukemia treatment with asparaginase, (iii) a Phase 2 dose-ranging pharmacodynamic study in critical COVID-19 patients and (iv) a Phase 2 trial in AKI with associated AHRF, called KOURAGE, expected to initiate in the first half of 2024. There are currently no approved therapies to treat either AP, AIPT or AKI. In previous trials, patients responded well to Auxora regardless of severity or cause of disease. CalciMedica is also exploring the potential of Auxora treatment for other acute indications including acute respiratory distress syndrome. About CalciMedica CalciMedica 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. 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 supporting the ongoing Phase 1/2 CRSPA AIPT study (called CRSPA – NCT04195347), with additional data expected by 2H 2024. CalciMedica plans to initiate its Phase 2 KOURAGE study in AKI in 1H 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 . Forward-Looking Statements This communication contains forward-looking statements which include, but are not limited to, statements regarding CalciMedica's planned and ongoing clinical trials and the timing, design, expected patient enrollment thereof and the expected timing for the release of data from those trials, including its planned Phase 2 KOURAGE trial of Auxora in AKI with associated AHRF, its ongoing Phase 2b trial of Auxora for AP with accompanying SIRS, its ongoing Phase 1/2 trial of Auxora in pediatric patients with AIPT, and its Phase 2 dose-ranging pharmacodynamic study in critical COVID-19 patients; the potential benefits of Auxora for the treatment of AKI, AP and AIPT; the potential of Auxora for the treatment of other acute indications including acute respiratory distress syndrome; the potential of CalciMedica's proprietary technology to provide therapeutic benefits in life-threatening inflammatory and immunologic diseases; pre-clinical and clinical studies of Auxora supporting the rationale for and design for the KOURAGE trial and the estimated patient population in the United States for AKI. 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 or preclinical studies may not be indicative of results that may be observed in the future; potential safety and other complications from Auxora; the scope progress and expansion of developing and commercializing Auxora; the size and growth of the market therefor and the rate and degree of market acceptance thereof; economic, business, competitive, and/or regulatory factors affecting the business of CalciMedica generally; CalciMedica's ability to protect its intellectual property position; and the impact of government laws and regulations. Additional risks and uncertainties that could cause actual outcomes and results to differ materially from those contemplated by the forward-looking statements are included under the caption "Risk Factors" in CalciMedica's Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 and elsewhere in CalciMedica's subsequent reports on Form 10-K, Form 10-Q or Form 8-K filed with the SEC from time to time and available at . These documents can be accessed on CalciMedica's web page at ir.calcimedica.com/financials-filings/sec-filings. CalciMedica Contact: Investors and Media Argot Partners Sarah Sutton/Kevin Murphy calcimedica@argotpartners.com (212) 600-1902 Company Codes: NASDAQ-NMS:CALC

An essential protein that acts as a gatekeeper for calcium entering cells promotes the growth of oral cancer and generates pain, according to a new study. Targeting this protein -- the ORAI1 calcium channel -- could provide a new approach to treating oral cancer, which causes persistent pain that worsens as it progresses. An essential protein that acts as a gatekeeper for calcium entering cells promotes the growth of oral cancer and generates pain, according to a new study published in Science Signaling led by researchers at NYU College of Dentistry. Targeting this protein -- the ORAI1 calcium channel -- could provide a new approach to treating oral cancer, which causes persistent pain that worsens as it progresses. "Our results show that the ORAI1 channel fuels the growth of oral cancer tumors and produces an abundance of molecules that, once secreted, interact with neurons resulting in an increased sensitivity to pain," said Ga-Yeon Son, a postdoctoral fellow in the Department of Molecular Pathobiology at NYU College of Dentistry and the study's first author. The keepers of the gates of heaven ORAI calcium channels -- named after the three sisters in Greek mythology who guarded the gates of heaven at Mount Olympus -- play an important role controlling how much calcium enters cells. "These calcium channels can be a source of good or bad for cells," said Rodrigo Lacruz, professor of molecular pathobiology at NYU College of Dentistry and the study's senior author. "Calcium entering cells is necessary for many good things, but too much calcium for a long time has the opposite effect." Calcium channels have been linked to various cancers, especially cancer progression, but few studies have looked at the role of ORAI1 in cancer and pain. "Calcium influx through ORAI1 channels has been well known to contribute to the regulation of gene expression by activating gene transcription factors in the cells. Notably, our investigation extends its function in regulating gene expression to altering oral cancer pain," said Son. Less ORAI1, less cancer growth and pain The researchers first analyzed tissue samples from human oral cancer tumors and healthy tongues. They found that the ORAI1 gene, which contains instructions for creating the ORAI1 calcium channel, was heavily overexpressed in the tumors but not in healthy tissue. They then examined human oral cancer cells and found that activating the ORAI1 calcium channel (but not other calcium channels) caused a large influx of calcium into cancer cells. This influx resulted in the increase of a calcium-dependent enzyme called matrix metalloprotease 1 (MMP1) that is secreted outside of cancer cells. MMP1 is abundant in multiple types of cancer, including oral cancer, where its overexpression is associated with metastasis and poor prognosis. Removing the ORAI1 gene from oral cancer cells changed the course of the disease in animal studies. When mice were inoculated with cancer cells lacking the ORAI1 gene, tumors grew more slowly and were less painful. "These findings demonstrate an important role for ORAI1 in oral cancer progression and pain, but what is the mechanism? We wondered if MMP1 could be the messenger relaying pain," said Lacruz. In collaboration with NYU Pain Research Center scientists Rajesh Khanna and Yi Ye, the team looked at the levels of MMP1 expressed in the fluid surrounding oral cancer cells and saw that cells lacking the ORAI1 gene secreted less MMP1 into the surrounding fluid. They combined the fluid with neurons from the trigeminal ganglia, a collection of nerves in the face that transmit pain in oral cancer. The fluid from cancer cells without the ORAI1 gene did not elicit a strong response from the neurons, but the MMP1-rich fluid from cells with ORAI1 evoked an increase in action potentials, the necessary signal for pain transmission. "This gives us evidence that an abundance of MMP1 may generate increased sensitivity to pain," said Lacruz. The researchers also ran experiments with abnormal but non-cancerous cells. When they overexpressed the ORAI1 gene in these non-invasive cells, they became invasive, raising the possibility that ORAI1 could play a role in cells switching from non-cancerous to cancerous cells. Future research: blocking ORAI Several FDA-approved drugs block the ORAI1 calcium channel, but they have not yet been tested in oral cancer. In future studies, the researchers will see whether nanoparticles can be loaded with an ORAI-blocking drug and precisely delivered into the tongues of animal models to stop oral cancer progression and pain. "In light of the ongoing opioid crisis, our study paves the way for validating novel pain treatments in oral cancer," said Rajesh Khanna, director of the NYU Pain Research Center, professor of molecular pathobiology at NYU Dentistry, and a co-author of the study. "Ultimately, our hope is that targeting the ORAI1 channel in oral cancer can prevent or delay the progression from oral epithelial dysplasia to oral cancer tumors and concurrently alleviate the pain burden experienced by oral cancer patients," added Son. Additional study authors include Nguyen Huu Tu, Maria Daniela Santi, Santiago Loya Lopez, and Guilherme H. Souza Bomfim of NYU College of Dentistry; Manikandan Vinu, Ariya Chaloemtoem, Rama Alhariri, and Youssef Idaghdour of NYU Abu Dhabi; and Fang Zhou of NYU Langone Health. The research was supported by the National Institute of Dental and Craniofacial Research (DE027981, DE027679, R01DE029493), National Institutes of Health HEAL Initiative (R01DE032501), National Institute of Neurological Disorders and Stroke (NS098772, NS120663), and National Institute on Drug Abuse (DA042852).