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 6 active drug repurposing programs. See below for more information on these programs in Every Cure’s Pipeline.
In the last 11 years, 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 (additional laboratory studies needed):
DL-alpha-difluoromethylornithine (DFMO) for Bachmann-Bupp syndrome (BABS)
The use of an enzyme inhibitor for a rare, genetic neurodevelopmental disorder is an active program at Every Cure. Building off of encouraging early off-label use, Every Cure is working to validate the mechanism, study the natural history, and prepare for a clinical trial to bring this potential therapy to more children in need.
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, Every Cure aims 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.
CLINICAL GEMS (additional clinical studies needed):
Coming soon!
UNSUNG HEROES (additional awareness and access needed):
Leucovorin for cerebral folate deficiency-associated autism spectrum disorder
The use of leucovorin for cerebral folate deficiency-associated autism spectrum disorder is an active program at Every Cure. Building on the foundational work of prior researchers, Every Cure is working to ensure that individuals who could benefit from this treatment are aware of it and have access. 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, Every Cure is 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.
Repurposing opportunity for major depressive disorder
Every Cure is working on a repurposing opportunity for Major Depressive Disorder. Building on a foundation of over a dozen clinical studies showing significant and clinically meaningful benefit, Every Cure is working to elevate awareness of this drug-disease pair across the healthcare community.
As part of its growing portfolio, Every Cure is exploring hundreds of repurposing opportunities every month with dozens undergoing further consideration, including one clinical gem and two repurposing opportunities in a hematological and a post-infectious condition.
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 characterized by inflammation, blood vessel damage, and progressive strokes. Etanercept, adalimumab, and infliximab are TNF inhibitors approved for the treatment of multiple autoimmune diseases, which were identified as a potential repurposed treatment for DADA2. Treatment of DADA2 patients with these TNF inhibitors has been groundbreaking, leading to improvements in clinical symptoms and a reduction in deadly strokes. Based on the role of etanercept as a life-saving treatment for DADA2 and evidence of its long-term efficacy from observational studies (Coarsi R et al.’s study; no clinical trials were performed), treatment guidelines were developed by Dr. Chip Chambers and the DADA2 Foundation (Lee P et al.’s international consensus statement) with guidance and support from Dr. David Fajgenbaum. Today, the vast majority of DADA2 patients around the world are effectively treated with TNF inhibitors.
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 unicentric Castleman disease (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-dexamethasone-thalidomide (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 unicentric Castleman disease (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.