Precision Glyco-Modulation of Macrophages with EF-M2 (ImmutalonTM) Improves Function and Lowers Inflammatory Biomarkers in Aging Dogs: A Double-Blind, Placebo-Controlled Trial
by
, ,
Evgeny Pokushalov
1,2,*
,
Dmitry Kudlay
3,4,
Claire Garcia
1,
John Smith
1,
Nikolai Revkov
5,
Anastasya Shcherbakova
6 and
Richard Miller
1 1
Scientific Research Laboratory, Triangel Scientific, San Francisco, CA 94101, USA
2
Center for New Medical Technologies, 630090 Novosibirsk, Russia
3
Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia
4
Institute of Medicine and Medical Technologies, Novosibirsk State University, 630090 Novosibirsk, Russia
5
VEGA Veterinary Clinic, 630049 Novosibirsk, Russia
6
BALTO Veterinary Clinic, 630055 Novosibirsk, Russia
*
Author to whom correspondence should be addressed.
Vet. Sci. 2025, 12(12), 1168; https://doi.org/10.3390/vetsci12121168
Submission received: 11 November 2025
/
Revised: 22 November 2025
/
Accepted: 6 December 2025
/
Published: 9 December 2025
(This article belongs to the Section Veterinary Internal Medicine)
Simple Summary
Older dogs often slow down and lose “vitality” because of low-grade, chronic inflammation. EF-M2 is a protein-based treatment designed to gently nudge immune cells called macrophages toward a calmer, repair-oriented state. In a randomized, double-blind, placebo-controlled study of 60 geriatric pet dogs (≥10 years), EF-M2 increased free-living activity and improved owner-reported vitality within a few weeks. On average, dogs receiving EF-M2 added about 23 more active minutes per day during the first treatment week compared with placebo, and they showed broader gains in a prespecified vitality score by day 28; side effects were uncommon and similar to placebo. Some benefits persisted for four weeks after the last dose. These results suggest that precisely targeting innate immunity may help older dogs stay more active and feel better, but longer studies are needed to confirm how durable the effects are and which dogs benefit most.
Abstract
We evaluated whether macrophage-targeted glyco-modulation can improve day-to-day function in aging companion animals. In a multicenter, randomized, double-blind, placebo-controlled trial, 60 client-owned geriatric dogs (≥10 years) received subcutaneous EF-M2 (0.1 μg/kg, every 72 h for 4 weeks; protocolized, blinded step-up to every 48 h at day 14 for partial responders) or matched placebo, followed by 4 weeks off-treatment. Two prespecified co-primary endpoints were tested hierarchically: change in accelerometer-measured active minutes/day at week 1 and change in a day-28 vitality composite (z-score of inverted CBPI-PSS, HRQL-vitality, and appetite VAS). EF-M2 was superior to placebo on both: +23.05 min/day at week 1 (95% CI, 18.16–27.94; p < 0.001) and +2.01 z-units at day 28 (95% CI, 1.52–2.50; p < 0.001). Key secondaries favored EF-M2, including greater week-4 activity (+33.00 min/day, 26.83–39.18; p < 0.001), lower BAER auditory threshold (−5.28 dB, −7.53 to −3.04; p < 0.001), and reduced transepidermal water loss (−1.35 g/m2·h, −2.45 to −0.25; p = 0.02); multiplicity was controlled with Holm–Bonferroni procedures. Owner-reported global improvement was more frequent with EF-M2 at day 28 (93.3% vs. 10.0%) and remained higher at day 56 off-treatment (50.0% vs. 16.7%). Prespecified pharmacodynamic markers shifted in directions consistent with M2-skewing (ARG1:iNOS ratio and IL-10 increased; TNF-α decreased) by day 7. Adverse events were infrequent, mild, and similar to placebo; no treatment-related withdrawals or serious events occurred. These findings support macrophage-targeted glyco-modulation as a promising approach to rapidly improve real-world activity and multidomain vitality in older dogs, with short-term signals persisting off-treatment; longer, adequately powered trials are warranted to define durability, structural outcomes, and phenotype-specific benefits.
