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A pro resolution lipid mediator for treatment of rheumatoid arthritis

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R44AR070686-01
Agency Tracking Number: R44AR070686
Amount: $1,500,000.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: NIAMS
Solicitation Number: PAR14-088
Timeline
Solicitation Year: 2014
Award Year: 2016
Award Start Date (Proposal Award Date): 2016-09-01
Award End Date (Contract End Date): 2019-08-31
Small Business Information
8 SOLVIVA RD
West Tisbury, MA 02575-1626
United States
DUNS: 833130045
HUBZone Owned: No
Woman Owned: Yes
Socially and Economically Disadvantaged: No
Principal Investigator
 PRAKASH JAGTAP
 (978) 969-3195
 jagtap@radikalrx.com
Business Contact
 ANDREW SALZMAN
Phone: (866) 925-2871
Email: salzman@radikalrx.com
Research Institution
N/A
Abstract

Radikal Therapeutics is developing the first therapeutic Resolvin molecule intended for the management of
rheumatoid arthritis RA Resolvins are endogenous picomolar potent small molecules that activate a
complex intracellular mechanism by which tissue inflammation is modulated and ultimately resolved Our
technical approach is supported by research demonstrating the utility of our candidate therapeutic Resolvin
R in reducing injury in clinically relevant rodent models of RA R is potentially superior to its
competitors by virtue of a novel mechanism of action distinct from existing therapies and those in
development and its ability to increase host immune defense as opposed to the more typical
immunosuppression that is associated with methotrexate calcineurin inhibitors and anti TNF
inhibitors Safety studies in rats dogs and humans do not reveal toxicity at doses logs in excess of the
intended therapeutic exposure Aim Establish the PK properties of enteral R including joint
tissue distribution following gavage delivery to mice with arthritis We will undertake a full analysis of the
PK profile of R Plasma and joint tissue concentrations of C labeled R will be measured
following administration to male SD rats with collagen induced arthritis A full PK profile of R will
be constructed Aim Scale up the synthetic route of R and generate batches sufficient for
primary reference standard and pharmacology studies To lower cost and allow for large scale
manufacturing RTX has invented a novel proprietary step synthetic route performed as a proof of
concept at a mg scale Even at this early stage the overall yield is and represents an improvement in
efficiency of over times that of any prior synthesis and a fold cost saving We now wish to utilize this
new synthesis as a platform for the production of gram amounts of research grade material in the first
instance and to develop this into a viable manufacturing process for g and ultimately kg amounts of R
We now propose to optimize our new process with the intent of achieving a further fold increase in
yield and elimination of half of the chromatographic isolation steps The campaign will include i
identification and improvement of those synthetic steps that are rate and or yield limiting ii
identification of those telescoping steps that do not require discrete purification of each intermediate iii
consideration of protection deprotection strategies and protecting groups iv assessment of the shelf life
use of unstable intermediates within an appropriate window v analysis of by products to understand and
reduce competing side reactions vi choice of reagents for scale up replace where possible with safe
routine cheaper reagents vii examination of alternatives to chromatographic separations viii
development of analytical methods for analysis of intermediates and relevant impurities ix generation of
multi g batches and x development of analytical methods for batch analysis and release of the API Existing therapies of rheumatoid arthritis provide many with only marginal relief and are often
ineffective We are developing a revolutionary approach to the medical management of refractory
rheumatoid arthritis based on the use of R that leverages the endogenous mechanism by
which inflammation is naturally resolved We now propose to carry out studies to define the
concentration of R in blood and joint tissue and to improve its manufacturing process so as
to reduce the cost of goods and thereby increase its commercial appeal

* Information listed above is at the time of submission. *

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