Every Cure’s Drug Repurposing Portfolio
Current Repurposing Programs and Previous Treatments Repurposed by Our Leadership
Every Cure is on a mission to save and improve lives by repurposing drugs. We utilize an AI platform to identify and advance the most promising drug repurposing opportunities. In less than one year since building the first version of our AI-powered platform and pipeline, we have 9 active drug repurposing programs. See below for more information on these programs in Every Cure’s Pipeline.
Dr. David Fajgenbaum, the co-founder and president of Every Cure, has advanced 14 repurposed treatments for conditions such as idiopathic multicentric Castleman Disease (iMCD), angiosarcoma, and DADA2 syndrome. See below for more information about these repurposed treatments.
Current Repurposing Programs:
FRONTIER EXPLORERS (Undertaking additional laboratory studies):
DL-alpha-difluoromethylornithine (DFMO) for Bachmann-Bupp syndrome (BABS)
Every Cure is collaborating with the researchers who first identified Bachmann-Bupp Syndrome (BABS), Dr. Andre Bachmann of Michigan State University, College of Human Medicine and Dr. Caleb Bupp of Corewell Health, on a repurposing opportunity with the drug DL-alpha-difluoromethylornithine (DFMO). BABS is a rare, genetic disorder that causes symptoms including neurodevelopmental delay, alopecia (hair loss), and hypotonia (poor muscle tone). DFMO (also known as eflornithine) has historically been used to treat African sleeping sickness and female facial hair growth, and it is currently approved for the prevention of recurrence of neuroblastoma. Building on encouraging off-label use and mechanistic experiments pioneered by Dr. Bachmann and Dr. Bupp, we aim to perform preclinical experiments further supporting the molecular underpinnings of this disease, a retrospective study of all identified patients to date, and prepare for a regulatory submission to bring this potential therapy to more children in need.
See key publications:
Repurposing eflornithine to treat a patient with a rare ODC1 gain-of-function variant disease
Lidocaine for localized cancers
The use of lidocaine is being investigated by Every Cure as a potential adjunct therapy to reduce recurrence and improve survival in patients with localized cancers or surgically resectable solid tumors. Building on clinical evidence from breast cancer studies, we aim to conduct studies to identify additional cancer types that may respond and to uncover the mechanisms by which lidocaine may inhibit tumor growth and metastasis.
See key publication.
Beta blocker for a rare neurodegenerative disease
The use of a beta blocker is being investigated by Every Cure as a potential therapy for a rare neurodegenerative disease. Early evidence suggests the drug may benefit patients by enhancing lysosomal function. We are conducting preclinical studies to validate these mechanisms and evaluate real-world evidence supporting its potential impact.
CLINICAL GEMS (Undertaking additional clinical studies):
Immunomodulator for a rare autoimmune skin disease
The use of an immunomodulator is being explored by Every Cure as a potential therapy for a rare autoimmune skin disease. Early clinical data, including more than a dozen case reports and multiple clinical trials, suggest potential benefit in reducing disease activity. We are conducting a meta-analysis of the existing clinical data to evaluate treatment effectiveness and guide the design of future clinical studies.
UNSUNG HEROES (Raising awareness and increasing access):
Folinic acid for cerebral folate deficiency associated with speech and other neurodevelopmental delays
The use of folinic acid for cerebral folate deficiency associated with speech and other neurodevelopmental delays is an active program at Every Cure. Building on the foundational work of prior researchers, we are working to ensure that individuals who may have cerebral folate deficiency are aware of the currently available blood test and have access to it to help guide treatment decisions by their medical providers. In parallel, the team is exploring ways to strengthen the evidence base through performing biomarker research and a potential Phase III clinical trial.
Lidocaine for breast cancer
The use of lidocaine for breast cancer is an active program at Every Cure. Building on the foundational work of prior researchers, we are working to ensure that the doctors and surgeons who would administer this treatment are aware of the evidence and able to access it. In parallel, the team is exploring opportunities to strengthen the evidence base by verifying existing data and assessing the potential for additional preclinical research.
Glabellar injection of Botox for major depressive disorder
Glabellar injection of Botox for major depressive disorder is an active program at Every Cure that builds on a foundation of over a dozen clinical studies showing a significant and clinically meaningful benefit.
Lenalidomide for a rare histiocytosis condition
Every Cure is pursuing a promising repurposing opportunity for lenalidomide in a rare histiocytosis condition. Building on evidence from a Phase II study and extensive case reports demonstrating safety and clinical benefit, we are working to raise awareness among clinicians and researchers about its potential for broader use in this rare disorder and to ensure that all patients who could benefit have access to the therapy.
As part of our growing portfolio, we are exploring hundreds of repurposing opportunities every month with dozens undergoing further consideration, including one other clinical gem.
Previous Treatments Repurposed by Our Leadership:
Sirolimus for idiopathic multicentric Castleman disease (iMCD)
Lead Investigator: Dr. David Fajgenbaum, University of Pennsylvania
Key Publications
Arenas D et al. Increased mTOR activation in idiopathic multicentric Castleman disease.
About:
Idiopathic multicentric Castleman disease (iMCD) is a rare and potentially fatal hematologic condition involving systemic inflammation and life-threatening multi-organ system dysfunction. Few treatment options existed in 2014. In 2014, Fajgenbaum identified mTOR as a novel therapeutic target through serum proteomics, flow cytometry, and immunohistochemistry and became the first Castleman patient ever to take sirolimus, an FDA-approved mTOR inhibitor, which was initially approved for organ transplant rejection. This discovery and the use of sirolimus in Dr. Fajgenbaum and two other patients was published in the Journal of Clinical Investigation. Fajgenbaum and his team performed additional studies to confirm heightened mTOR activation in other iMCD patients (Arenas et al, Blood, 2020). This led to the launch of an NIH-funded clinical trial and the inclusion of sirolimus in iMCD treatment guidelines.
TNF inhibitor (etanercept, adalimumab, or infliximab) for DADA2
Leader(s): Dr. Chip Chambers, DADA2 Foundation
Key Publications:
Coarsi R et al. Long-term efficacy of etanercept in ADA2 deficiency
About
Deficiency of Adenosine Deaminase 2 (DADA2) is a rare and life-threatening genetic disorder that primarily causes severe inflammation and damage to blood vessels leading to early strokes, but it can also present with immunodeficiency and bone marrow failure. By chance, doctors discovered that tumor necrosis factor (TNF) inhibitors—medications such as Etanercept, Adalimumab, and Infliximab, already approved for multiple autoimmune diseases—could be repurposed to treat DADA2. This breakthrough has been transformative: not a single patient treated with TNF inhibitors has suffered a stroke since starting therapy, an unprecedented result in rare disease care. Because the evidence is so strong, clinical trials were never conducted and likely never will be. Building on this discovery, treatment guidelines were developed by Dr. Chip Chambers and 38 world-wide experts on DADA2, together with the DADA2 Foundation, through an international consensus guidelines (Lee P. et al.) with support from Dr. David Fajgenbaum. Today, most patients with DADA2 worldwide are effectively treated with TNF inhibitors, giving them safer and healthier lives.
Rituximab for iMCD
Leader (s): Drs. Frits van Rhee, Corey Casper, David Fajgenbaum, Kazu Yoshizaki, Castleman Disease Collaborative Network
Key Publications
Liu A et al. Idiopathic multicentric Castleman’s disease: a systematic literature review
About
Idiopathic multicentric Castleman disease is a rare and potentially fatal hematologic condition involving systemic inflammation and life-threatening multi-organ system dysfunction with limited treatment options. Fajgenbaum and his team published a study in Lancet Haematology in 2016 that identified the presence of autoantibodies in iMCD patients, implicating B cells as a potential therapeutic target and rituximab as a potential treatment. Fajgenbaum worked with collaborators to perform retrospective evaluations of iMCD patients treated with rituximab, revealing a role for rituximab which was reported in the Annals of Hematology in 2018. Despite the lack of dedicated clinical trials for rituximab in iMCD, rituximab was included as a second-line therapy in the iMCD treatment guidelines.
Siltuximab for unicentric Castleman disease (UCD)
Leader (s): Drs. Frits van Rhee, Corey Casper, David Fajgenbaum, Kazu Yoshizaki, Castleman Disease Collaborative Network
Key Publications:
Yoshizaki K et al. Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease
Zhang M et al. UCD with MCD-like inflammatory state: surgical excision is highly effective
About:
Unicentric Castleman disease (UCD) is a subtype of Castleman Disease which involves a single enlarged lymph node or multiple enlarged lymph nodes within a single lymph node station. While interleukin-6 (IL-6) has been known to play a key role in multicentric Castleman disease (MCD) for years, Fajgenbaum collaborated with Lu Zhang and colleagues in 2021 study in Blood Advances which identified cases of UCD with an MCD-like inflammatory state, suggesting common biological behavior and possibly a role for IL-6. Based on anecdotal data from siltuximab in unresectable UCD, Fajgenbaum and colleagues advocated for the inclusion of siltuximab in international evidence-based guidelines for unresectable UCD.
Rituximab for UCD
Leader (s): Drs. Frits van Rhee, Corey Casper, David Fajgenbaum, Kazu Yoshizaki, Castleman Disease Collaborative Network
Key Publications:
About:
Unicentric Castleman disease (UCD) is a subtype of Castleman Disease which involves a single enlarged lymph node or multiple enlarged lymph nodes within a single lymph node station. Rituximab has demonstrated potential in iMCD as a second- and third-line treatment and is actively used in cases of iMCD where siltuximab is ineffective or unable to be utilized. Based on work done by Fajgenbaum and colleagues, rituximab in the setting of unresectable UCD was included in international evidence-based guidelines for UCD.
Carfilzomib-cyclophosphamide-dexamethasone for POEMS syndrome
Leader(s): Dr. David Fajgenbaum, University of Pennsylvania
Key Publications:
About: POEMS syndrome is a rare paraneoplastic disorder involving monoclonal plasma cells, debilitating neuropathy, and life-threatening multi-organ system dysfunction with limited treatment options. Carfilzomib-cyclophosphamide-dexamethasone is a treatment often used for multiple myeloma. Given the similarities between multiple myeloma and POEMS syndrome and a high score for these agents and related agents in an early version of Every Cure’s algorithms, carfilzomib-cyclophosphamide-dexamethasone was administered to a POEMS patient in January 2024 who was getting ready to go onto hospice care, which ultimately saved his life (NYT link here). In Summer 2024, this treatment approach was described by a separate group in a conference research article.
Velcade-cyclophosphamide-dexamethasone (VCD) for iMCD
Lead Investigator: Drs. Lu Zhang, Jian Li (Peking Union University Medical Center), and David Fajgenbaum, University of Pennsylvania
Key Publications
Liu A et al. Idiopathic multicentric Castleman’s disease: a systematic literature review
Fajgenbaum D. HHV-8-negative/idiopathic multicentric Castleman disease UpToDate Guidelines
About
Idiopathic multicentric Castleman disease (iMCD) is a rare and potentially fatal hematologic condition involving systemic inflammation and life-threatening multi-organ system dysfunction with limited treatment options. Fajgenbaum and his team published a study in Lancet Haematology in 2016 that identified the presence of autoantibodies in iMCD patients, implicating B cells as a potential therapeutic target and Velcade (bortezomib), a plasma cell inhibitor, as part of a combination therapy with Cytoxan (cyclophosphamide) and dexamethasone, known as VCD, which was initially approved for multiple myeloma. A clinical trial by Fajgenbaum and colleagues in Zhang et al (Leukemia & Lymphoma, 2022) highlighted improvements in iMCD patients treated with VCD. VCD has been included in UpToDate guidelines for iMCD treatment.
Thalidomide-cyclophosphamide-prednisone (TCP) for iMCD
Lead Investigator: Drs. Lu Zhang, Jian Li (Peking Union University Medical Center), and David Fajgenbaum, University of Pennsylvania
Key Publications
Liu A et al. Idiopathic multicentric Castleman’s disease: a systematic literature review
Fajgenbaum D. HHV-8-negative/idiopathic multicentric Castleman disease UpToDate Guidelines
About
Idiopathic multicentric Castleman disease is a rare and potentially fatal hematologic condition involving systemic inflammation and life-threatening multi-organ system dysfunction with limited treatment options. Fajgenbaum and his team published a study in Lancet Haematology in 2016 that identified the presence of autoantibodies in iMCD patients, implicating B cells as a potential therapeutic target and thalidomide, a plasma cell modulator, along withCytoxan (cyclophosphamide) and prednisone (TCP regimen). This regimen was initially approved and utilized in multiple myeloma. A clinical trial performed by Fajgenbaum and colleagues (Zhang et al, Blood, 2019) reported patient improvement. TCP has been included in UpToDate guidelines for iMCD treatment.
Daratumumab for POEMS syndrome
Leader(s): Dr. Frits van Rhee and David Fajgenbaum, Castleman Disease Collaborative Network
Key Publications
Khan M et al. Daratumumab for POEMS Syndrome
About
POEMS syndrome is a rare paraneoplastic disorder involving monoclonal plasma cells, debilitating neuropathy, and life-threatening multi-organ system dysfunction with limited options. Given the important role that plasma cells play in POEMS syndrome and the fact that daratumumab, a monoclonal antibody against CD38 that is FDA approved for the treatment of multiple myeloma, is effective at eliminating plasma cells, Drs. van Rhee and Fajgenbaum decided to try daratumumab in a POEMS syndrome patient who responded well.
Sirolimus for UCD
Leader(s): Drs. Frits van Rhee and David Fajgenbaum, Castleman Disease Collaborative Network
Key Publications:
About:
Unicentric Castleman disease (UCD) is a subtype of Castleman Disease which involves a single enlarged lymph node or multiple enlarged lymph nodes within a single lymph node station. After Fajgenbaum and colleagues demonstrated the potential of sirolimus in iMCD, they investigated its role in unresectable UCD, demonstrated its effectiveness in the first unresectable UCD patient treated, and included it in international evidence-based guidelines for UCD.
Ruxolitinib for iMCD
Lead Investigator: Dr. David Fajgenbaum, University of Pennsylvania
Key Publications
About
Idiopathic multicentric Castleman disease (iMCD) is a rare and potentially fatal hematologic condition involving systemic inflammation and life-threatening multi-organ system dysfunction with limited treatment options. In 2021 Fajgenbaum and colleagues discovered that the JAK/STAT pathway is a key therapeutic target for iMCD, which was highlighted in Pierson et al, Blood Advances, 2021). This led to ruxolitinib, a JAK inhibitor initially approved for myelofibrosis, to be identified as a promising treatment for iMCD and the first iMCD patient treated with ruxolitinib (Lust et al, Pediatric Blood Cancer, 2021). Currently, the Center for Cytokine Storm Treatment & Laboratory (CSTL) is spearheading the launch of a clinical trial to further assess ruxolitinib’s effectiveness in iMCD.
Eculizumab for iMCD
Leader(s): Dr. David Fajgenbaum, University of Pennsylvania
Key Publications
Wing A et al. Transcriptome and unique cytokine microenvironment of Castleman disease
About:
Idiopathic multicentric Castleman disease (iMCD) is a rare and potentially fatal hematologic condition involving systemic inflammation and life-threatening multi-organ system dysfunction with limited treatment options. In 2018, Fajgenbaum and colleagues discovered complement activation as a potential therapeutic target in iMCD (Pierson et al, AJH, 2018). This led to the identification of eculizumab, a C5 inhibitor initially approved for Myasthenia Gravis. A separate study also involving Dr. Fajgenbaum also identified a complement signature from transcriptomic analyses (Wing et al). Based on these findings, the first few iMCD patients were given eculizumab in 2020, with their progress being documented in the University of Pennsylvania’s Castleman disease patient registry.
Adalimumab for iMCD
Leader(s): Dr. David Fajgenbaum, University of Pennsylvania, and Luke Chen, UBC-Vancouver
Key Publications
About
Idiopathic multicentric Castleman disease is a rare and potentially fatal hematologic condition involving systemic inflammation and life-threatening multi-organ system dysfunction with limited treatment options. In 2023, Fajgenbaum and colleagues combined together results from serum proteomics analyses, in vitro studies, and an early version of Every Cure’s AI platform to identify TNF as a novel therapeutic target. Adalimumab, an anti-TNF agent which is FDA-approved for conditions such as rheumatoid arthritis, was utilized in a highly treatment refractory patient, who has been in remission for over two years. This case was published in the New England Journal of Medicine.
Pembrolizumab for angiosarcoma
Lead Investigator(s): Jung Ryul Kim and Kyu Yun Jang, Chonbuk National University Medical School, Korea
Key Publications
Sindhu S et al. Angiosarcoma treated successfully with anti-PD-1 therapy – a case report.
von Mehren M et al. Soft Tissue Sarcoma, Version 2.2022
About
Angiosarcoma (AS) is a rare and deadly cancer that forms in the lining of blood vessels and lymph vessels. In 2016, metastatic angiosarcoma was considered a uniformly fatal condition. However, an important study was performed by Kim (PLOS ONE, 2013) on five AS patients, which highlighted increased PDL1 staining in 4 of 5 AS patients. Though PDL1 expression can often indicate that a PD1 inhibitor may be effective, there had been no published instances in 2016 of AS patients being treated with an approved PD1 inhibitor such as pembrolizumab, which was initially approved for melanoma. When Dr. Fajgenbaum encountered a patient in 2016 with metastatic AS who was out of options, he requested PDL1 staining, which confirmed increased expression and, in a pioneering approach, treated an AS patient with the PD1 inhibitor pembrolizumab. Remarkably, as of 2025, this patient has remained in remission for over 9 years, and many more patients have been treated successfully with this treatment. The promising outcomes have since led to multiple clinical trials investigating PD1 inhibitors for AS and the recommendation of PD1 inhibitors for AS in NCCN Guidelines marking a significant shift in the treatment paradigm for this aggressive cancer.
