Septic Shield

Many hospitalized COVID-19 patients experience an overactive immune response consisting of cytokine dysregulation, and increase in inflammatory myeloid cells that infiltrate the lung and other tissues, leading to tissue damage, microthrombosis, acute respiratory distress syndrome (ARDS), multiple organ failure, and ultimately death.  Recognition and mitigation of the host inflammatory components of these COVID-19 pathophysiological conditions could lead to improved patient outcomes. 

Our proposal focuses on an important cytokine mediator of inflammatory cascades.   Cytokines have several pro-inflammatory functions, and these functions have been implicated ARDS, and Sepsis.  Interfering with these proinflammatory functions by turning the cytokines themselves into Trojan horses for small-molecule, anti-inflammatory drug delivery could be of benefit to individuals with complications associated with pathological immune responses observed in COVID-19, ARDS, Septic shock and Sepsis.

Our fully synthetic, non-peptide anti-inflammatory agents will moderate host reactions at the early stages of a cytokine storm and prevent disease progression.

The problem that we are trying to solve is: how do we put the brakes on a cytokine storm before it becomes a runaway bus resulting in significant damage to the host as seen in COVID-19, and Sepsis?

Currently, there are 3.7 million people afflicted with COVID-19.  This illness will severely afflict roughly 15% of infected people, and approximately seven percent will die from Septic-like host responses unless new solutions are implemented.  Alarmingly, one out of five deaths worldwide is caused by such host-inflammatory reactions - more than by cancer. Most cases were in poor and middle-income countries, but even wealthier nations are dealing with Sepsis.  COVID-19 has simply shined additional light on this ever-growing problem.

We believe our unique approach will be a highly efficient, cost-effective, and predictable path forward for creating clinically significant therapeutics to benefit COVID-19 afflicted patients.  Our approach harnesses the proinflammatory cytokines to allow preferential access of our bifunctional small molecule conjugates into cells contributing to the excessive host inflammatory response, which is damaging the lungs and other tissues in severe COVID-19 cases. This work represents a creative leap forward in the development of innovative and more accurate anti-inflammatory drugs.

Utilizing endogenous proteins as Trojan horses to bring drugs of interest into actual target cells is a cost-effective approach.  We can make our drug conjugates for as little as $9/mg. 

 Accurate placement of an anti-inflammatory agent to, and into, immune cells may allow a more personalized and precise treatment opportunity.

The broader impact/commercial potential of this project is to develop a novel, cost-effective, small molecule delivery platform technology to address the dominating problem of misplaced drugs and the resultant off-target effects in the clinical translation of emerging therapeutics.  You don’t have to be a rocket scientist to think that anti-inflammtory drugs should target immune cells or that anti-cancer drugs should track with some selectivity to cancer cells.

Currently, 95.6% of drug assets targeting the autoimmune and inflammation market do not successfully translate to markable drug.   This lack of translation is a significant systemic cost burden in cancer research, which dominates the final cost of therapeutics.  There is a critical need to identify improved design elements and predictable assays early in drug development, which will more accurately place drug payloads within targeted cells.  Such predictive design elements should improve the translation rate of small-molecule drugs of all types going forward.

Apart from the tragic human consequences of the COVID-19 coronavirus epidemic, the current costs of COVID-19 treatments are substantial.  Hospitalized individuals with severe COVID-19 cases may face charges as high as $34,000 to $73,000 with an average hospital stay of six days.  The financial toxicity and financial distress associated with out-of-pocket costs of these treatments will cause considerable monetary problems for many patients who are primarily elderly and may have already had other ongoing health issues. 

    Hospitals are struggling to cover the ~$42 Billion in costs of uninsured individuals as a growing role of unemployment leaves almost 13.5 million individuals without any insurance coverage.   While Health and Human Services are expected to cover the cost of treating these individuals, the federal budget will be stretched with these HHS reimbursement costs.  Despite these enormous expenditures, the resolution of severe COVID-19 cases remains uncertain.  New cost-effective treatments are urgently needed.

Our low-cost solution could be implemented before progression to severe disease. 

     When designing the next generation of small-molecule drugs, we are simply stating that one of the design elements that need to be built into a new candidate molecule is: The ability to be preferentially enriched in target cells. Current small-molecule drugs are missing such design elements. 

New drugs are challenged to focus their attention on target cells and remain unpredictable in the clinic.  Building translational predictability into the structure of small-molecule drugs is a cost-effective solution moving forward.  The economic benefits of adopting our approach could be substantial to patients and payers alike independent of the wealth of their nations.

The Problem:  What if 95% of NASA's rockets failed to launch or if only 5% of Boeing's planes made it off the runway?  I believe a new design plan would be called for immediately.

Unfortunately, ~95% of new drug development programs do not succeed in producing marketable compounds.  With the cost of a developmental failure for a new drug in the $650 Mil. to $1.6 Bn. range,  a new design for small molecule drugs is urgently needed.  

The Solution: At RJSBIO, we have created a new design format for anti-inflammatory drugs and cancer drugs. We recognize that current small-molecule drugs have essentially no cellular selectivity and remain reliant solely on target selectivity for activity.  Many, if not most, current small-molecule drugs are using serendipity to find their destination cells. This lack of cellular selectivity is an obvious design flaw.  

You don’t have to be a rocket scientist to think that anti-inflammatory drugs should go to immune cells.  Cancer drugs should go to cancer cells. 

You may be shocked to hear that some of the cancer drugs we work with are preferentially localized to the skin where they cause horrific rashes.

 When designing the next generation of small-molecule drugs, we are simply stating that one of the design elements that need to be built into a new candidate molecule is: The ability to be preferentially enriched in target cells. 

RJS Bio has retained strong general counsel to set up and manage our intellectual property portfolio. Our initial patent, US 2015/0352217, published December 10, 2015, entitled Pharmaceutical Compounds Targeted by MIF Affinity-Tethered Moieties, covers a diversity of MIF affinity moiety species within a defined affinity-tethered genus. We have already been awarded patent protection as both a US utility patent application and a PCT foreign application that discloses and claims a genus of tether moiety species and discloses the key tethered products (tether plus optional short linker plus active cytotoxic moiety) where there is strong in vitro comparison data as between each cytotoxic moiety in both its naked and tethered form. On a molar basis, the tethered molecules are much more potent.  We are creating a strong patent portfolio using a product-based approach.

    Our patenting strategy provides much higher IP portfolio value for potential large Pharma developmental partners. Moreover, our tethered products can provide novel compositions of matter even when the cytotoxic or imaging moiety may be known and could also be still protected in an enforceable claim of a third party. Our product-focused IP strategy creates both freedom to operate even when using third-party cytotoxic agents and creates novel compositions of matter for RJSBio because the tether is covalently bonded to the cytotoxic agent and is not a prodrug delivery vehicle (in contrast to ADC’s or antibody-drug conjugates).

    We believe the present IP patent portfolio provides a significant and uniquely strong portfolio in the developing chemotherapy and diagnostic market segments.

Our research and development efforts began with the creation of
prototypical cancer drugs developed under a State of Washington LSDF grant, and we continued with the support of the National Science Foundation SBIR Phase I for our tumor imaging efforts. 

Prototypical drugs were developed by conjugating a cytokine-binding moiety
with a diversity of payload moieties, including cancer drug payloads such as
Doxorubicin, Artemisinin, EGFRi, and tumor imaging payloads (DOTA). In this COVID-19 application, we will continue to develop the delivery platform, and we will focus on blunting immune cell functionality.

The Problem:  What if 95% of NASA's rockets failed to launch or only 5% of Boeing's planes made it off the runway?  What if 95% of packages delivered by Amazon fell on the wrong doorstep?   Clearly, a new design plan would be called for immediately.

Unfortunately, 95% of drug development programs do not succeed in producing marketable compounds.  With the cost of a developmental failure for a new drug in the $650 Mil. to $1.6 Bn. range,  a new design for small-molecule drugs is urgently needed.  This failure rate is unacceptable and the cost burdens are transferred to individuals. 

The Solution: At RJSBIO we have created a new design format for drugs. We recognize that current small-molecule cancer drugs have essentially no cellular selectivity and remain reliant solely on target selectivity for activity.  Many, if not most, current small-molecule cancer drugs are using serendipity to find their destination cells. This is an obvious design flaw in need of a creative solutions.  

If properly funded we could serve a global population within 5 years.

We need to fund IND-enabling pharmacology, DMPK & toxicology studies on our new compounds in preparation for regulatory approval. 

We are actively seeking funding to accomplish this task. 

Our major barrier remains funding.

We have assembled a talented technicial team to accomplish the requisite tasks to commercialize our project.  

The next major tasks are in vivo evaluation of our prototypes and expansion of the our payload sets. 

We do our best to keep moving forward despite our financial limitations.   

It is our hope that the positive press offered by the MIT SOLVE program would help bring additional financial resources to our efforts. 

Also, I would love to detail to the press the unbelievable nonsense we have encountered while seeking federal funding for our program through the National Cancer Institute.  MIT solve could do more to cure cancer by cleaning house at the center for scientific review, than by funding any individual program. 

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1 full time

8 part time

We also employ a cadre of CRO firms as our budget allows. 

Our team has extensive experience in drug development with over 16 INDs under our belts.

We work with several Universities around the United States under fee for service contracts.

Business model:  Our flexible semi-virtual business model allows us to be very resource-efficient while maintaining a low overhead.  With funding, we transiently assemble the required team needed to complete the next step of our development.  Our approach is a nimble, cost-effective proposal.  Moreover, we believe third-party validation of our critical data is a key component of hitting our desired commercial milestones.

     We have demonstrated our platform technology adds significant cellular selectivity (20X to 40X) to payloads derived from well-studied, economically validated, and clinically important cancer drugs such as Doxorubicin and EGFRi. The serious adverse events associated with the parental molecules justifies a closer examination of structural components of these cancer drugs.  We believe this preliminary data also warrants further investigation of our approach to creating new drugs to combat COVID-19 associated inflammatory events.

   Our modular approach generates new chemical entities through covalent modifications well-validated target binding domains, each with potential for new intellectual property surrounding the unique composition of matter.  Notably, this is not a pro-drug approach, and the release of our drug delivery moiety is not required for the drug to retain its original target-binding function. We are covalently adding layers of targeting/cellular selectivity during the synthesis of our precision compounds.  Our initial customers include; industrial collaborations, academic/medical collaborators, VCs, and federal granting agencies. 

As an emerging biotechnology company, we have a finite amount of financial resources.  We generally receive highly favorable scientific comments from potential partners and investors. Still, these comments also come with requests for definitive in vivo studies and even completion of IND enabling experiments before further commitments can be made.  

For this reason, we've approached federal funding programs to establish the requisite in vivo studies, which would allow RJS to entice private investments. 

Our focus on the development of tumor imaging agents as the proximal
product for our research will enable us to make good progress forward under our present financial constraints.  We are a small, fully independent organization, and we are dedicated to conducting genuinely innovative research in the area of drug delivery.  We mitigate our risks with the use of well-seasoned talent and creative collaborations. 

I am applying to Solve because our cost-effective solutions should be brought forward.

MIT Solve may assist in bringing much needed resources to our campaign.

When viewed as a whole, entering a competitive therapeutic market can be daunting for a small company. 

    When the COVID-19 market is viewed through RJSBIO’s lens, the possibility of creating new compositions of matter capable of cellular precision with higher dosing with reduced side effects using clinically validated payload moieties is an attractive high-value proposition.  RJSBIO also believes compounds created on our innovative drug delivery template will have a competitive price point advantage over other macromolecular approaches and biologicals.  

We could use assistance in growing our platform and connecting with funding streams.  

 As an emerging biotechnology company, we have a finite amount of financial resources.  We generally receive highly favorable scientific comments from potential partners and investors. Still, these comments also come with requests for definitive in vivo studies and even completion of IND enabling experiments before further commitments can be made. 

We seek alignment with organizations that may assist with these early POC studies. 

Apart from the tragic human consequences of the COVID-19 coronavirus epidemic, the current costs of COVID-19 treatments are substantial.  Hospitalized individuals with severe COVID-19 cases may face charges as high as $34,000 to $73,000 with an average hospital stay of six days.  The financial toxicity and financial distress associated with out-of-pocket costs of these treatments will cause considerable financial problems for many patients who are primarily elderly and may have already had other ongoing health issues. 

    Hospitals are struggling to cover the ~$42 Billion in costs of uninsured individuals as a growing role of unemployment leaves almost 13.5 million individuals without any insurance coverage.   While Health and Human Services are expected to cover the cost of treating these individuals, the federal budget will be stretched with these HHS reimbursement costs.  Despite these enormous expenditures, the resolution of severe COVID-19 cases remains uncertain.  New treatments are urgently needed.

    The timeline to progression for COVID-19 patients from the onset of symptoms is 7-9 days before progression, where a severe case would be considered for hospital admission and therapeutic intervention.  Early symptoms are generally mild but may progress rapidly.  Our focus on mitigating the cellular infiltrates required to sustain and promote an inflammatory cascade could be a cost-effective path forward for COVID-19 therapeutic development.   Preventing the progression of COVID-19 from a mild cold to a severe form of ARDS could save roughly 90% of the current hospital expenditures.