# Development of a non-Factor small molecule, oral, prophylactic and hemostasis balanced therapy for treatment of clotting disorders including hemophilia A/B

> **NIH NIH R43** · YEWSAVIN, INC. · 2022 · $300,000

## Abstract

ABSTRACT
Hemophilia, A, B, C, and vwF are inherited bleeding disorders resulting from a partial or complete deficiency of
Factor VIII (FVIII) or Factor IX (FIX), respectively. Factor-based therapies involve the administration of
exogenous clotting factor concentrates with the aim of achieving the necessary levels of circulating protein.
However, factor-based therapies present the complication of inhibitors (antibodies) inactivating the therapeutic
agents, rendering treatments ineffective. Current investigational therapies seek to diminish the anti-clotting
natural control factors Protein C, Anti-thrombin and Tissue Factor Protein Inhibitor (TFPI-inhibitor) in order to
enhance clotting in patients with impaired clotting. This approach has significant challenges since the coagulation
process must remain extremely well-balanced and is important to make sure that prevention of hemorrhage by
enhancing clotting does not result in inadvertent thrombosis. Furthermore, most of these therapies are
administered in bi-weekly injections, subcutaneous or intravenous, and adverse events relating to injectables
remain a concern.
Our overarching goal was to understand the remarkable effects of traditionally used plant extracts on wound
healing and the balance between hemostasis and thrombosis, and their application in developing an oral
treatment for hemophilia. YewSavin’s plant-derived pair of coagulant and anti-coagulant molecules result in the
best balance of hemostasis and thrombosis. This small molecule oral, the first in such class, treatment
strategy, two Complementary Components (CC_2), consisting of Chalcones (pro-coagulant) and Flavones (anti-
coagulant), that could potentially revolutionize hemophilia and anti-thrombotic treatments for clotting and
thrombotic disorders alike by promoting blood clotting processes without causing thrombosis.
In preliminary studies, bio-assays of clotting and healing times guided our initial fractionation assays towards
identifying single molecule entities that promoted clotting and healing. We triangulated molecules for hemophilia
treatment and accelerated healing using our proprietary artificial intelligence (AI), structure match (SAR), and
experimental verification by bioassay guided fractionation ability. Using a Factor VIII knockout (KO) mouse
model, we demonstrated that our identified CC_2 molecules cause significant improvement in clotting time, in
normal rats and in Factor VIII KO mice. These results demonstrate that CC_2 is not Factor VIII dependent and
is also more efficient than the first line therapy currently used, injection of Factor VIII. Finally, there are currently
no known anti-thrombin small molecule agents. According to our preliminary results, the mechanism of action
seems to be the dose-dependent reversal of the Heparin-Antithrombin complex that blocks coagulation.
This project proposed by YewSavin, Inc. will apply knowledge of clotting processes gained from plant
molecules to address the challenges ...

## Key facts

- **NIH application ID:** 10384995
- **Project number:** 1R43HL162336-01
- **Recipient organization:** YEWSAVIN, INC.
- **Principal Investigator:** Makarand Prabhakar Gore
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2022-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10384995

## Citation

> US National Institutes of Health, RePORTER application 10384995, Development of a non-Factor small molecule, oral, prophylactic and hemostasis balanced therapy for treatment of clotting disorders including hemophilia A/B (1R43HL162336-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10384995. Licensed CC0.

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