CoREST KMGDs
LeadFirst-in-class molecular glue degraders
MPNs · AML · Thymic rejuvenation
Established in vivo PoC; advancing toward development candidate selection.
ProgressLead Optimization
DiscoveryLead Opt.IND-EnablingPhase 1/2
First-in-class CoREST Degraders
Targeting diseases to the core
RejuvenRx leverages world-leading expertise in stem cell biology to develop disease-modifying medicines in hematology, oncology and aging — with first-in-class CoREST molecular glue degraders and an initial focus on myeloproliferative neoplasms and thymic rejuvenation.
Founded in 2020 by Prof. Guy Sauvageau & Anne Marinier, Université de Montréal
The Challenge
A profound unmet need across blood cancers and aging
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.
No curative therapies
For myeloproliferative neoplasms, allogeneic stem cell transplantation is the only curative option — with limited applicability. Current therapies manage symptoms with minimal impact on disease progression.
Immune decline with age
Thymic involution erodes immune competence, leaving patients vulnerable after hematopoietic cell transplantation and in age-related immune decline. No approved therapy restores it.
High and rising prevalence
MPNs affect approximately 300,000 individuals in the US alone, with roughly 12,000 new cases each year — a large population with insufficient long-term control.
Our Solution
The power of CoREST degradation
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.
- New, orally bioavailable CoREST molecular glue degraders (KMGDs) dosed systemically to treat patients in vivo — developed in-house with academic labs.
- A distinct chemical class from UM171, the ex vivo molecule licensed to ExCellThera. We build on that validated CoREST biology rather than the asset itself.
- A differentiated profile over LSD1 inhibitors — selectivity, context-dependency and reversibility — for a wider therapeutic window.
The Science
In vivo precision medicine rooted in stem cell biology
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
CoREST — a master regulator of stem cell fate
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, identifying CoREST as a key driver of stem cell aging and a compelling therapeutic target.
The Mechanism
A validated molecular glue 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. It is the proof of mechanism for our program.
KBTBD4 Molecular Glue Degraders are referred to as KMGD.
The Difference
Beyond LSD1 inhibition
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.
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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
Proof of concept, not bioavailable
UM171 was the first-generation CoREST degrader and proof of mechanism — but it is not orally bioavailable, so it can only be used ex vivo to expand cord-blood stem cells in a dish. That mechanism underpins Zemcelpro® (EU-approved) and is licensed to ExCellThera. RejuvenRx does not develop the ex vivo asset.
KMGDs — in vivo
Developed at RejuvenRx
New, orally bioavailable CoREST degraders dosed systemically to treat patients directly — advanced with academic labs. A distinct chemical class, not the ex vivo molecule.
![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
Confidential scientific detail
Confidential Deep Dive
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Pipeline
A focused lead asset and a scalable platform
Our CoREST program anchors the pipeline while the molecular glue platform extends into additional oncology targets sharing the same chemistry and mechanism.
Cyclin K degrader
Best-in-class molecular glue degrader
Triple-negative breast cancer (TNBC)
Differentiated degrader series expanding the platform into solid tumors.
ProgressLead Optimization
DiscoveryLead Opt.IND-EnablingPhase 1/2
ETC1 modulators
OXPHOS / cancer metabolism
Pancreatic cancer
Differentiated modulators of oxidative phosphorylation and cancer metabolism.
ProgressDiscovery
DiscoveryLead Opt.IND-EnablingPhase 1/2
Programs
Three programs, one molecular glue platform
A first-in-class lead program anchors the pipeline while our platform chemistry extends into additional oncology and metabolism targets.
Lead
CoREST KMGDs
First-in-class KBTBD4 molecular glue degraders
Our anchor program: orally bioavailable KBTBD4 molecular glue degraders (KMGDs) that selectively dismantle the RCOR1–LSD1–HDAC (CoREST) complex, built on the clinically validated UM171 biology.
Target indications
MPNs · AML · Thymic rejuvenation
Development stageLead Optimization
DiscoveryLead Opt.IND-EnablingPhase 1/2
- Established in vivo proof-of-concept in HSC expansion and an AML model
- Differentiated from catalytic LSD1 inhibitors — selective complex degradation
- Advancing toward development candidate selection within 6–12 months
Cyclin K degrader
Best-in-class molecular glue degrader
A differentiated Cyclin K degrader series extending the molecular glue platform into solid tumors, leveraging the same chemistry expertise behind the CoREST program.
Target indications
Triple-negative breast cancer (TNBC)
Development stageLead Optimization
DiscoveryLead Opt.IND-EnablingPhase 1/2
- Differentiated degrader series with best-in-class potential
- Expands the platform beyond hematology into solid tumors
- Shared discovery engine and molecular glue know-how
ETC1 modulators
OXPHOS / cancer metabolism
Novel modulators of the electron transport chain (ETC1) targeting oxidative phosphorylation and cancer metabolism in tumors with high metabolic dependency.
Target indications
Pancreatic cancer
Development stageDiscovery
DiscoveryLead Opt.IND-EnablingPhase 1/2
- Differentiated mechanism targeting OXPHOS-dependent tumors
- Addresses a high unmet need in pancreatic cancer
- Earliest-stage program with platform optionality
Main Indications
Two lead programs, one shared biology
A single CoREST-targeting mechanism addresses both the malignant progenitors driving blood cancers and the regenerative decline behind immune aging.
01
Thymus Rejuvenesce
Restoring immune competence lost after transplantation and during aging 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 — including T-cell receptor excision circles (TRECs), CD4+ T-cell counts, TCR repertoire diversity, and total lymphocyte counts — will establish early biomarkers of biological activity and guide subsequent clinical development.
Immune reconstitutionAging biologyPost-HCT
02
Myeloproliferative Neoplasms
A lead program targeting PV, ET 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 across a $3B+ addressable market.
PV · ET · MFLead program$3B+ TAM
Market Opportunity
A $3B+ opportunity built in phases
A focused lead asset delivers near-term value while a scalable platform opens significant upside across hematology, oncology and aging.
Near Term
$3B+ TAM
Lead Asset — MPNs
- Post-JAK MF / PV / ET with 500k+ addressable patients globally
- Recurring revenue from chronic oral therapy
- Clear regulatory and reimbursement path
Mid Term
$3B+ TAM
Line Extensions — Hematologic Malignancies
- Selected AML subsets and high-risk myeloid diseases
- Designed for combination with standard therapies
- Premium per-patient economics (160k globally)
Long Term
New Market Creation
Platform Upside — Immune & Aging Biology
- Thymic rejuvenation to restore immune competence post-HCT
- Sickle cell disease (HbS) potential
- Potential first-in-class therapeutic category
Leadership Team
World-leading expertise in stem cell biology
A team of scientists and operators who discovered UM171 and have spent decades translating stem cell biology into medicines.
Christine MartensMSc, MBA
President of the Board
Executive leader with broad experience guiding life sciences organizations through strategy, growth and governance.
Anne MarinierPhD
CEO & Board Member
Over 25 years in drug discovery and development. Co-founded and led IRIC’s Drug Discovery Unit and identified UM171.
Guy SauvageauMD, PhD
CSO & Board Member
Internationally recognized stem cell biologist and hematologist. Identified UM171 and co-founded IRIC and the Quebec Leukemic Cell Bank.
EM
Eric MatelCFA
CFO
25+ years of expertise across business strategy, operations, corporate finance and financial markets.
David MilletteCA, CPA, CFA
Board Member
Over 20 years of business management and advisory experience in life sciences — financial, legal and strategic.
SP
Stéphane PelusoPhD
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.
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Scientific Advisory Board
Frederic CharronPhD
Professor, McGill University & Université de Montréal
Expert in neurobiology.
Lambert BusqueMD, FRCPc (Hematology)
Professor of Medicine, Université de Montréal
Expert in myeloproliferative disorders and clonality studies, including TCR, BCR and hematopoietic stem cells.
Natasha SzuberMD, FRCPc (Hematology)
Assistant Professor of Medicine, Université de Montréal
Expert in clinical trials for myeloproliferative neoplasms (MPN).
Investors
A capital-efficient path to first-in-class value
RejuvenRx is raising a $5M seed round to advance our lead CoREST program to development candidate selection within 6–12 months, operating on a lean, milestone-driven model.
De-risked biology
Built on clinically validated UM171 / CoREST biology, with in vivo proofs-of-concept in HSC expansion and an AML model.
First-in-class chemistry
Proprietary, orally bioavailable KBTBD4 molecular glue degraders (KMGDs) — a differentiated mechanism beyond LSD1 inhibition.
Large, phased market
A $3B+ near-term opportunity in MPNs, with platform upside across hematologic malignancies, oncology and aging biology.
World-class team
Founded by the discoverers of UM171, supported by an experienced board and a specialist scientific advisory board.
$5M
Seed round or strategic partnership
We welcome conversations with investors and strategic partners aligned with our mission of adding life to years and years to life.
Use of proceeds
- 1
Development candidate selection
Advance CoREST KMGDs to DC nomination
- 2
IND-enabling studies
Initiate tox and CMC readiness
- 3
Platform expansion
Progress Cyclin K and ETC1 programs
About Us
Deep biological validation, first-in-class chemistry, a capital-efficient path
RejuvenRx is seeking a $5M seed investment or strategic partnership to advance the CoREST program to development candidate selection within 6–12 months, with a lean operating model aligned to IND-stage biotech execution.
- 2020
- Founded by Prof. Sauvageau & Marinier at Université de Montréal
- $3B+
- Total addressable market across MPNs and hematologic malignancies
- 2
- De-risking in vivo proofs-of-concept — HSC expansion and AML model
Targeting diseases to the core
We welcome conversations with investors, strategic partners and clinical collaborators who share our mission of adding life to years and years to life.