John Mumm

30-year scientist-founder. CSO @ChronicleBio (AI for ME/CFS & Long COVID). Ex-CEO Deka Bio. Founder ARMO, acq. by Lilly $1.6B. DNAX, Stanford, MD Anderson PhD.

[John Mumm @Mummsthewurd]

Our goal at ChronicleBio is to discover the underlying biology that drives complex chronic illnesses and develop treatments to improve the lives of people suffering from these conditions.

There is one thing we think is important in conversations like this: conditions like ME/CFS probably aren’t one disease process happening identically in every patient or even consistent during the progression of the disease. Patients often report that the symptoms they currently have are not the same as those they experienced years before.

We treat them as heterogeneous conditions and are discovering multiple biological subtypes or endotypes, like recent publications detailing immunological stratification [1,2,3,4].

This heterogeneity explains what patients have experienced and clinicians have reported for years: the same treatment can provide significant benefit for one person and do almost nothing for another with the same diagnosis.

That can look like medicine failing, especially in the setting of a clinical trial. But it may also mean we’re treating patients with mechanistically different disease biology as though they’re the same.

Part of that heterogeneity may not just be betweenpatients, but within a patient's disease course. Patients with these conditions experience symptoms that overlap substantially with those experienced by patients with autoinflammatory and autoimmune diseases.

Our model: heterogenous immune dysregulation unfolds over time and can involve different parts of the immune system at different stages [2,3]. By identifying each patient's stage, we can treat individual patients with the therapeutics that are most likely to help.

One system where that heterogeneity shows up clearly is the microvasculature, an underappreciated part of this story that deserves serious attention.

There's evidence for endothelial dysfunction [5], altered microvascular regulation and tissue perfusion [8], platelet hyperactivation [6], and coagulation abnormalities [7].

IgG immune complexes in ME/CFS patients and those with post-infectious conditions are enriched for hemostasis, platelet activation and fibrin clot pathways [9].

Hyperactive platelets can bind circulating immune complexes through their FcgRIIa [10] surface receptors, which primes them for degranulation. In the microvasculature the local shear environment itself can drive platelet aggregation via von Willebrand factor mediated adhesion [11,12]. So, a primed platelet population and an inflamed microcirculation can compound each other.

We are actively investigating whether ME/CFS patients exhibit increased immune aggregates of neutrophils, antibody and platelets to determine whether there is a causal link between the immune system and microvascular clotting.

Where we’d be more cautious is in declaring any one of these mechanisms the upstream cause.
Immune dysregulation, autonomic dysfunction, metabolism, endothelial biology, platelets, coagulation, and tissue perfusion don’t operate independently. They interact and potentially reinforce each other.

So maybe the more useful question isn’t:
“Is this an immune disease or a vascular disease?”
It’s:
“Which mechanisms are driving disease in which patients? Which are upstream vs downstream? How do they interact? And can we identify biological subtypes that predict who will respond to which treatment?”

That’s where we think a lot of the opportunity is.
The microvasculature may be a major piece of the puzzle. But understanding how it fits with immune, autonomic, and metabolic dysfunction across different patient subtypes is the harder, and more important, question.

Patients have been describing this complexity for decades. We built ChronicleBio to to turn it into treatments that bring real relief to them and their families.

Some useful papers:
[1] Dudova et al., Int J Mol Sci (2026). DOI: 10.3390/ijms27010268
[2] Rohrhofer et al., J Clin Med (2024). DOI: 10.3390/jcm13010275
[3] Bastos et al., J Immunol (2025). PMID: 40373264
[4] Identifying subtypes of Long COVID: a systematic review, eClinicalMedicine. PMID: 41509610
[5] Sandvik et al., PLoS ONE (2023). DOI: 10.1371/journal.pone.0280942
[6] Nunes et al., Pharmaceuticals (2022). DOI: 10.3390/ph15080931
[7] Nunes et al., Blood Reviews (2023). DOI: 10.1016/j.blre.2023.101075
[8] Wirth & Löhn, Medicina (2024). DOI: 10.3390/medicina60020194
[9] Liu et al., Brain Behav Immun Health (2026). DOI: 10.1016/j.bbih.2026.101187
[10] Apostolidis et al., Front Immunol (2022). DOI: 10.3389/fimmu.2022.834988
[11] Nesbitt et al., Nat Med (2009). DOI:10.1038/nm.1955
[12] Springer TA, Blood (2014). PMID: 24928861

[John Mumm @Mummsthewurd]

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