Who else is working on this
Which laboratories and companies hold which piece of the problem, what they have shown, and where the open ground is. Read this as a collaboration map, not a competitor list.
Two properties are left off the chart on purpose. Every one of these entries carries published counter-evidence, and every one records its own open questions — both are requirements of the schema rather than findings, so a bar for either could not move, and a statistic that cannot move cannot tell you anything. 35 of 36 additionally carry a bite_back note, which is required only where an entry touches an intervention.
Biomea Fusion — icovamenib (BMF-219): the covalent menin inhibitor that left oncology for diabetes
Biomea Fusion made a menin inhibitor that binds its target irreversibly, and originally tested it in leukaemia. Both of its cancer trials have been terminated and every study the company is now running is in type 2 diabetes, so as a leukaemia partner it has effectively left the field.
Children's Oncology Group — the trial network, the AALL protocol series and the biobank that no single lab can substitute
The Children's Oncology Group is the network through which almost all childhood cancer trials in North America are run, and it holds the specimens those trials collect. For a rare disease like infant leukaemia it matters more than any individual laboratory, because it is the only structure that can assemble enough patients to answer a question at all.
Collaborate or compete: an honest matrix, including where the lab would be duplicating a better-resourced effort
Not everyone in this field is a potential partner, and some of what the lab might do is already being done better elsewhere. This entry says plainly which is which.
Eytan Stein (MSKCC), Ghayas Issa (MD Anderson) and the clinical menin-inhibitor investigator network
A small number of adult-leukemia doctors at big American cancer centres run essentially every menin-inhibitor trial. They decide which combinations get tested and in whom, and almost none of their studies enrol infants.
Johnson & Johnson / Janssen — bleximenib (JNJ-75276617): paediatric from age 2, but not infants, and the dedicated child study was withdrawn
Johnson & Johnson's menin inhibitor bleximenib is the only one whose company-run first-in-human trial openly enrols children, but the floor is two years old, which excludes infants. A separate paediatric combination study the company registered was withdrawn before enrolling anyone.
Jolanta Grembecka & Tomasz Cierpicki (University of Michigan) — the chemistry that made the menin interface druggable
Two chemists in Michigan made the first small molecules that block the grip between menin and MLL, and solved the crystal structure showing how. Everything in the clinic today descends from that chemistry.
Kathrin Bernt (University of Pennsylvania / Children's Hospital of Philadelphia) — DOT1L and H3K79 methylation in KMT2A-rearranged leukemia
Bernt proved that KMT2A-rearranged leukemia depends on one specific chemical mark placed on DNA-packaging proteins by an enzyme called DOT1L. That discovery produced the first targeted drug tried in this disease, and its clinical disappointment is one of the most instructive failures in the field.
Kotecha group, Perth: the infant KMT2A-rearranged laboratory this graph had cited once
A research group in Perth, Australia publishes more preclinical work on infant KMT2A-rearranged leukaemia than almost anyone, and until this cycle this project had cited it essentially not at all. Reading it turned up two studies the graph had written off as unreadable and a third whose title contradicts an assumption running through the whole project.
Kura Oncology — ziftomenib (KO-539): an adults-only sponsor that quietly supplies infant trials
Kura owns ziftomenib, the second menin inhibitor approved by the FDA, but its licence and every trial Kura itself runs are restricted to adults aged 18 and over. The route to children, and to infants specifically, is indirect: Kura supplies the drug to academic trials it does not sponsor, including an infant leukaemia study.
Mel Greaves (Centre for Evolution and Cancer, ICR London) — natural history, in-utero origin and the prevention question
Greaves showed that childhood leukemia usually starts before birth and argues that the common form of it may be preventable by getting the infant immune system the microbial exposure it evolved to expect. His framework is why anyone thinks about prevention at all.
Michael Cleary (Stanford) & Akihiko Yokoyama (National Cancer Center, Tsuruoka) — the groups that discovered the menin requirement itself
In 2005 this pair showed that MLL fusion proteins must physically grip menin in order to cause leukemia at all. Every menin inhibitor in the clinic today exists because of that single result.
NCI TARGET — a finished paediatric leukaemia genomics resource, not an active partner
TARGET was a national programme that sequenced the genomes of thousands of children with leukaemia and other cancers, and its data still sits in a public archive anyone can apply to use. It is not an organisation you can collaborate with any more; it is a completed dataset with a front door.
Pablo Menendez & Clara Bueno (Josep Carreras Leukemia Research Institute, Barcelona) — cellular origin, fetal models and infant-specific drug resistance
This Barcelona group asks which cell the t(4;11) translocation has to happen in for leukemia to follow, and builds human stem-cell and fetal models to test it. They are also the group most willing to publish results that do not work.
Patricia Ernst (University of Colorado) — what normal KMT2A and menin actually do, which is the therapeutic-window question
Ernst studies what the normal, unbroken versions of these genes do in healthy blood. That matters because a drug that blocks the fusion also hits the normal machinery, and her work is the main reason to think menin can be blocked without wrecking blood production.
Rob Pieters, Inge van der Sluis & the Interfant consortium (Princess Maxima Center, Utrecht) — the only global infant-ALL trial network
Infant leukemia is so rare that no single country has enough patients to run a trial. Interfant is the international consortium that solved that, and it controls essentially every infant with this disease who is enrolled in a study anywhere.
Rolf Marschalek & Claus Meyer (DCAL, Goethe-University Frankfurt) — the world's KMT2A breakpoint dataset
A single laboratory in Frankfurt has sequenced the exact DNA break point in more KMT2A-rearranged leukemia patients than everyone else combined, because for twenty years the world has been sending them samples for diagnosis. If you want to ask any question about where the break happens, you have to go through them.
Scott Armstrong & Andrei Krivtsov (Dana-Farber / Boston Children's) — the group that turned menin dependency into a drug
This Boston group showed that KMT2A-rearranged leukemia is a distinct disease and then did the mouse and patient-sample work that made menin inhibitors real drugs. They are the most established competitor and the most valuable potential ally in this space at the same time.
St. Jude Cloud and the Pediatric Cancer Genome Project — raw paediatric leukaemia genomes a small lab can get without a collaboration
St. Jude runs a cloud platform holding raw genome and RNA sequencing data from more than ten thousand children with cancer, and any researcher can browse it for free and request the underlying data through a signed agreement. It is the one resource on this list a lab can start using this week without knowing anybody.
Sumitomo Pharma — enzomenib (DSP-5336): one trial, adolescents at 12 years and 40 kg, no paediatric programme
Sumitomo Pharma is developing enzomenib, a menin inhibitor in a single large phase 1/2 trial. The trial's normal age limit is 18, relaxed to 12 for teenagers weighing at least 40 kg at some sites, so children and infants are out of scope entirely.
Syndax Pharmaceuticals — revumenib (SNDX-5613), the only menin inhibitor licensed down to infancy
Syndax owns revumenib, the first menin inhibitor approved by the FDA, and it is the only one licensed for children as young as one year old. Its main trial has enrolled patients from 30 days of age, which makes Syndax the single most plausible industry partner for a lab working on infant leukaemia.
The second ring — smaller KMT2A-fusion mechanism labs, and where the literature actually points
Beyond the handful of famous groups there is a second ring of smaller laboratories, each owning one specific piece of KMT2A biology. These are the realistic partners for a small lab, because they need collaborators as much as we do.
Thomas Milne (MRC WIMM, Oxford) — MLL-AF4 target biology, enhancer architecture and PROM1/CD133
Milne's group in Oxford works out exactly which genes the MLL-AF4 fusion switches on and how it physically loops DNA to do it. Their discovery that the fusion drives CD133 has already become a CAR-T target.
Who holds the data and samples we cannot generate ourselves — an access map
A small lab cannot create infant leukemia patients, twenty years of DNA breakpoints, or a global trial cohort. This entry lists who does hold those things, what exactly they hold, and how hard it is to get.
AMLSG 23-14 / Palbo-AL-1 (NCT02310243) — the only trial ever run in MLL-rearranged acute leukemia with a CDK4/6 inhibitor, and it reported nothing
A German study gave the breast-cancer drug palbociclib to adults whose leukemia carried the KMT2A (MLL) rearrangement — the only trial ever done that matches this exact disease and this exact drug class. It was due to finish in 2019 and has never posted a single result.
AUGMENT-101 (NCT04065399) — the registration trial, and what 22.8% actually means
AUGMENT-101 is the trial that got the first menin inhibitor approved. Roughly two thirds of patients responded in some way, but only about one in five reached the strict definition of remission the approval was based on.
COG AALL0631 — lestaurtinib in infant KMT2A-rearranged ALL: negative overall, positive where the drug actually hit
This trial added a FLT3-blocking drug to chemotherapy for babies with KMT2A-rearranged leukemia. Overall it did not help, but the babies in whom the drug measurably switched FLT3 off did far better, which suggests the idea was right and the drug was too weak.
COG AALL15P1 — azacitidine epigenetic priming in infant KMT2A-rearranged ALL: on-target, well tolerated, no survival effect
Infant KMT2A-rearranged leukemia cells have too many chemical tags silencing their DNA, so this trial gave a drug that strips those tags off before each round of chemotherapy. The drug did exactly what it was meant to do to the DNA, was safe, and did not help the babies live longer.
COG AINV18P1 (NCT03792256) — palbociclib is deliverable in children with relapsed ALL, at 50 mg/m² for 21 days
A Children's Oncology Group study added the cell-cycle drug palbociclib to standard re-treatment chemotherapy in twelve children and young adults whose leukemia had come back. It was tolerated, it produced a dose that can be used in children, and five of them went into complete remission.
Counted absence: no menin-inhibitor trial has ever reported a response RATE in NUP98-rearranged patients
Three big trials of menin-blocking drugs deliberately let in patients whose leukaemia is driven by a NUP98 fusion, and one of them has a cohort built exactly for them. None has ever published how often those patients responded, and neither approved drug's label mentions NUP98 at all.
Interfant-06 — 651 infants, and the definitive answer that myeloid-style consolidation does not help
Interfant-06 is the chemotherapy plan most babies with KMT2A-rearranged leukemia are still treated on. Its main experiment — swapping in AML-style drug blocks after induction — made no difference, and overall survival did not improve compared with the previous protocol.
Interfant-21 (NCT05327894) — the randomised test of blinatumomab in infant KMT2A-rearranged ALL, open now
Interfant-21 is the worldwide trial running right now for babies under one year with KMT2A-rearranged leukemia. It is the experiment that will show whether the striking blinatumomab results were real.
Interfant-99 — the first global infant ALL protocol, and the first negative answer on myeloid intensification
Interfant-99 was the first time doctors worldwide treated babies with leukemia on one shared plan, so the results could actually be compared. It showed that adding extra AML-style chemotherapy at the end of treatment did not help at all.
NCT05631574 (COVALENT-102): the third solid-tumour menin-inhibitor trial, missing from this graph because its drug is called BMF-219 - terminated after 13 patients for a strategic reason, explicitly NOT for efficacy or safety
A covalent menin-blocking drug was tested in lung, pancreatic and bowel cancers driven by a KRAS mutation. The company closed the study after thirteen patients because it decided to stop working on cancer with this drug altogether, and it stated that neither safety nor lack of benefit caused the closure.
No menin-inhibitor or DOT1L-inhibitor trial has ever named this fusion - and the DOT1L trials excluded it by construction
We checked the eligibility rules of every major menin-blocking drug trial and both DOT1L-blocking drug trials. None mentions CALM-AF10. Worse, the DOT1L trials required an '11q23' chromosome break, which this fusion does not have - so the drug that should work here was never given to these patients.
POE 10-03 / NCT01319864 — the only completed paediatric trial of niche disruption, which mobilised blasts 3.4-fold and produced three responses in nineteen children, none of them in ALL
This was the one completed children's trial that tried to treat leukaemia by knocking cells out of their bone-marrow hiding place before giving chemotherapy. The drug did exactly what it was supposed to do biologically — it pushed leukaemia cells out into the bloodstream — but only three of nineteen heavily pretreated children responded, and none of them had lymphoblastic leukaemia.
SAVE (NCT05360160): the first prospective menin-inhibitor trial to report a NUP98-rearranged subgroup outcome
In a 42-patient trial of a menin-blocking drug combined with two other oral drugs, nine patients had leukaemia driven by a NUP98 gene fusion, and they did respond. But their remissions lasted about half as long as those of the other patients.