Discoveries

1) Caspase inhibitors as host targeted therapy in COVID19 and RNA viruses:

The first description of elevated Caspase-1 levels and the role of pyroptosis in COVID19

patients. This finding has led to designing of a clinical trial to assess Caspase inhibition as a

potential treatment modality in COVID19. The Phase 1 study showed safety and signals of

efficacy in outpatient mild COVID19

Kroemer A, Khan K, Plassmeyer M, Alpan O, Haseeb MA, Gupta R, Fishbein TM.

Inflammasome activation and pyroptosis in lymphopenic liver patients with COVID-19. J

Hepatol. 2020 Jul 6: S0168-8278(20)30437-2.

Premeaux TA, Yeung ST, Bukhari Z, Bowler S, Alpan O, Gupta R, Ndhlovu LC. Emerging

Insights on Caspases in COVID-19 Pathogenesis, Sequelae, and Directed Therapies. Front

Immunol. 2022 Feb 21; 13:842740.

Plassmeyer M, Alpan O, Corley MJ, et. al. Caspases and therapeutic potential of caspase

inhibitors in moderate-severe SARS-CoV-2 infection and long COVID. Allergy. 2022

Jan;77(1):118-129.

2) Discovery of a disease-modifying treatment for Food Protein–Induced

Enterocolitis Syndrome (FPIES)

The FPIES discovery is that a pathway-targeted biologic, dupilumab (an IL-4Rα blocker

approved for eczema, asthma, etc.), can unexpectedly switch off food-triggered FPIES-type gut

reactions in a subset of patients.

It began with a single “experiment of nature”: a patient with lifelong, severe wheat-induced

FPIES who, after starting dupilumab for eczema, accidentally ingested large amounts of wheat

and had no reaction—then reliably relapsed when dupilumab was stopped and improved again

when it was restarted. We then identified additional patients with FPIES or FPIES-like food-

triggered enterocolitis who showed the same pattern: sustained tolerance to previously

offending foods while on dupilumab, with recurrence of symptoms when the drug was

withdrawn.

Together, these cases strongly suggest that at least one endotype of FPIES is driven by a type-

2 cytokine/OX40L-linked pathway that is druggable with IL-4/IL-13 blockade, opening the door

to the first mechanism-based therapy (and biomarker-guided stratification) for this historically

untreatable, non-IgE food allergy.

Matthew Plassmeyer, Ph.D. Naomi Enav,Michael Girgis, Ph.D., Mikell Paige, Ph.D., Linda Todd,

 RNP, Laureana Israni, Oral Alpan, M.D. Dupilumab Opens a Therapeutic Window in Food

Protein Induced Enterocolitis Syndrome by un-licensing dendritic cells

https://www.jaci-global.org/article/S2772-8293(25)00193-6/fulltext

3) Basophils as Biosensors:

The basophil activation test (BAT) functions as a living biosensor for allergens by using

basophils from highly sensitized and reactive patients. We name this approach as

In BAT, fresh whole blood is exposed in vitro to candidate allergens—foods, drugs, or

formulas—and basophil up-regulation of activation markers such as CD63 is quantified by flow

cytometry. Because the readout is a functional response (degranulation/activation) instead of

just the presence of IgE, BAT can distinguish clinically relevant allergens. This makes BAT an

ideal biosensor platform to compare unknown or engineered products (e.g., hypoallergenic

formulas, new food ingredients) against known controls, detect trace allergen contamination,

and, in our work, provide a regulatory-grade in vitro alternative or adjunct to risky oral

challenges.

We are working with one of our partners to help reshape the U.S. regulatory pathway for

hypoallergenic infant formulas, using this process to support hypoallergenic labeling claims.

Capabilities

Ø All phases of clinical trials

Ø No CRO support needed for the proof-of-concept studies

Ø Research and CLIA/CAP lab to support all functional biomarkers studies

Ø Discovery

Ø Intellectual Property

Ø Blood draw capabilities across USA (Quest)

Ø Robust Patient Recruitment resources

Ø Active Clinical Immunology Clinic

Intellectual Property (published cases)

Postural Orthostatic Tachycardia Syndrome and CRTH2. Application #: 17/440620.

Filing date: 9/17/2021

Treatment for Diseases Caused by RNA Viruses. Application #: 17/919020. Filing date:

10/14/2022

Treatment for diseases caused by RNA virus SARS-CoV-2. US12377127B2. Active.

Expiration: 04-14-2041

Time Dependent Response of Basophils to Allergens, Application #: 18/213,417. Filing

date: 23 Jun 2023