RejuvenRx leverages world-leading expertise in stem cell biology to develop disease-modifying medicines in hematology, oncology and aging.
Its first-in-class CoREST molecular glue degrader initially focuses on myeloproliferative neoplasms and thymic rejuvenation.
Founded in 2020 by Prof. Guy Sauvageau & Anne Marinier, Université de Montréal
The dysregulation of hematopoietic stem cells sits at the root of myeloproliferative neoplasms and the erosion of immune function with age. Existing options fall short of modifying the underlying disease.
For myeloproliferative neoplasms (MPNs), allogeneic stem cell transplantation is the only curative option, with limited applicability. Current therapies manage symptoms with minimal impact on disease progression.
Thymic involution erodes immune competence, leaving patients vulnerable to cancer, infections and chronic diseases. No approved therapy currently restores it.
By degrading the CoREST complex, our molecular glues rejuvenate the blood system, reprogramming primitive myeloid progenitors and unlocking disease-modifying potential that enzymatic inhibition alone cannot reach.
Our approach targets the CoREST complex, the epigenetic hub governing blood stem cells, through molecular glue degradation validated across peer-reviewed research and the clinic.
The Target
The CoREST complex (RCOR1/3, LSD1 and HDAC1/2) is a central epigenetic regulator that controls hematopoietic stem cell self-renewal, lineage commitment and differentiation through coordinated histone demethylation and deacetylation. Research from the Sauvageau laboratory has revealed that aged hematopoietic stem cells display a profoundly altered CoREST1 transcriptional and chromatin accessibility signature compared with young stem cells (see deep dive), identifying CoREST as a key driver of stem cell aging and a compelling therapeutic target.
The Mechanism
UM171, discovered in the Sauvageau and Marinier labs, is a context-dependent, KBTBD4-recruiting degrader that removes CoREST subunits only within the complex, confirmed by cryo-EM. This is supported by various literature papers, which validate the mechanism.
KBTBD4 Molecular Glue Degraders are referred to as KMGD.
The Difference
LSD1 inhibitors validate the biology but enzymatic-only inhibition leaves room to improve. KMGDs offer superior selectivity, context-dependency and reversibility for a wider therapeutic window.
Unlike catalytic LSD1 inhibitors, which inhibit LSD1 activity irrespective of its binding partners and consequently perturb multiple LSD1-dependent regulatory complexes, CoREST degraders selectively dismantle the RCOR1–LSD1–HDAC complex. This approach abolishes both the enzymatic and scaffolding functions of LSD1 specifically within CoREST while preserving LSD1 functions in non-CoREST complexes, including NuRD and nuclear receptor-associated transcriptional programs. By targeting a discrete epigenetic repressor complex rather than the enzyme itself, CoREST degradation is predicted to achieve more selective chromatin remodeling with an improved therapeutic index.
UM171 — the prototype
Validated mechanism, limited to ex vivo use
UM171 is the first-generation CoREST degrader that established proof of mechanism for the platform. Its lack of oral bioavailability limits its use to ex vivo expansion of cord-blood stem cells in a dish. This validated biology underpins Zemcelpro® (EU-approved) and is licensed to ExCellThera. RejuvenRx does not develop the ex vivo asset.
KMGDs: Next-generation in vivo therapeutics
Developed at RejuvenRx
RejuvenRx is developing a new class of orally bioavailable CoREST degraders (KMGDs) designed for systemic administration and direct treatment of patients. A distinct chemical class from UM171, translating its validated CoREST biology from an ex vivo approach into in vivo therapeutic applications.
Thymus rejuvenation with CoREST degraders
CoREST degraders restore the immune shield by rejuvenating thymic function and re-establishing healthy T-cell production. Two complementary modalities share this biology: UM171, the ex vivo cell-therapy leader that drives rapid immune reconstitution, enhanced TCR diversity and restored immune tolerance in transplant settings; and UM626, an orally bioavailable analog that delivers in situ thymic rejuvenation without complex cell manufacturing — extending the approach to aging, immunosenescence and autoimmunity through simple, non-invasive dosing.
UM171 — ex vivo cell therapy
UM626 — oral in situ rejuvenation
![3D ball-and-stick molecular model of UM171, a pyrimido[4,5-b]indole with benzyl, methyltetrazole and aminophenyl-amino substituents](/images/um171-3d.png)
UM171 is the non-bioavailable prototype of CoREST degraders discovered by our academic founders.
Deep Dive
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Our CoREST platform anchors a broader pipeline expanding into additional oncology indications driven by stem cell biology.
First-in-class oral KBTBD4 molecular glue degraders
MPNs · AML · Thymic rejuvenation
Our anchor program: KBTBD4 molecular glue degraders (KMGDs) that selectively dismantle the RCOR1–LSD1–HDAC (CoREST) complex, built on the clinically validated UM171 biology.
Differentiated molecular glue degrader series
Solid tumors
A differentiated Cyclin K degrader series extending the pipeline into solid tumors and leveraging the chemistry expertise and molecular glue know-how established through the CoREST program.
Differentiated mechanism targeting OXPHOS-dependent tumors
Pancreatic cancer
Addresses a high unmet need in pancreatic cancer and provides platform optionality.
Our lead CoREST degrader program targets a fundamental CoREST-dependent epigenetic mechanism that drives both stem cell aging and myeloproliferation. By selectively dismantling the CoREST complex and restoring healthy epigenetic regulation, a single biological mechanism supports two therapeutic opportunities: hematologic malignancies and immune rejuvenation through restoration of thymic function.
Restoring immune competence lost after transplantation, aging, cancer therapy, and other settings associated with impaired lymphopoiesis and immune decline by rejuvenating the lymphoid potential of aged hematopoietic stem cells that seed the thymus, rather than by targeting the thymic microenvironment itself. In contrast to therapies that rejuvenate the thymic epithelium ("soil"), KBTBD4 molecular glue degraders (KMGDs) rejuvenate the hematopoietic stem cell "seed," restoring the production of lymphoid progenitors capable of repopulating the thymus. Exploratory Phase 0 endpoints will establish early biomarkers of biological activity and guide subsequent clinical development.
A lead program targeting Polycythemia Vera, Essential Thrombocythemia and Myelofibrosis where no curative drug exists. With established in vivo proof-of-concept, our oral CoREST degrader aims for rapid disease-modifying clinical signal, initially in post-JAK2 patients.
A team of scientists and operators who discovered UM171 and have spent decades translating stem cell biology into medicines.
President of the Board
Executive leader with broad experience guiding life sciences organizations through strategy, growth and governance.
CEO & Board Member
Over 30 years in drug discovery and development experience spanning industry (Bristol-Myers Squibb) and academia. Co-founded and led IRIC’s Drug Discovery Unit and identified UM171.
CSO & Board Member
Internationally recognized stem cell biologist and hematologist. Identified UM171 and co-founded IRIC and the Quebec Leukemic Cell Bank.
CFO
25+ years of expertise across business strategy, operations, corporate finance and financial markets.
Board Member
Over 20 years of business management and advisory experience in life sciences — financial, legal and strategic.
Advisor
Over 20 years in oncology R&D and BD. Previously CSO at Infinity Pharmaceuticals and Global Head of Oncology External Innovation at Ipsen Bioscience.
Professor, McGill University & Université de Montréal
Expert in neurobiology.
Professor of Medicine, Université de Montréal
Expert in myeloproliferative disorders and clonality studies, including TCR, BCR and hematopoietic stem cells.
Assistant Professor of Medicine, Université de Montréal
Expert in clinical trials for myeloproliferative neoplasms (MPN).
We welcome conversations with investors, strategic partners and clinical collaborators who share our mission of adding life to years and years to life.
