CNS AND ONCOLOGY DRUG CANDIDATES

Doctors know how they can improve their patients’ standard of care.

All the current drug candidates in our pipeline have emanated from deep dive into understanding the gaps the physicians face in their everyday SOC for patients. After developing the linker technology from concept to realization, we took the potential of our technology to the physicians. We prioritized our pipeline based on our discussions with KOLs and practicing neuro-oncologists, pulmonologists, immuno-oncologists and endocrinologists. This has resulted in first-in-class and best-in-class products that cater to improved efficacy, reduced toxicity as well as addressing unmet clinical needs.

Linker Enzyme Substrate System  or LESS^TM
Increases a drug’s therapeutic window by:

1. Targeting the drug to desired tissue, including brain across the Blood Brain Barrier

2. Releasing the Active drug in the target tissue by selective, local enzymatic cleavage

3. Reducing systemic toxicities by naturally degrading the Prodrug before releasing the active drug when not in its target tissue

This would at the least result in improving the standard of care (SOC) outcome in patients. Application of our technology would also open up new treatment regimen, especially in clinically unmet areas.

PROBLEM

Currently, there are many drugs that lack the ability to target disease specific tissues.

While Antibody Drug Conjugate (ADC) technology has addressed some of these shortcomings, it has not been able to solve the toxicity associated with the drug payloads that get released from the circulating ADCs in the plasma.

Then, there are highly efficacious drugs, which cannot be used because of their severe long-term and/or short-term toxicities.

Another major challenge not well resolved even after decades of research and clinical efforts is the ability to take efficacious drugs to brain across an uncompromised Blood-Brain barrier (BBB).

OUR SOLUTION

Praesidia has developed chemical linkers that convert drugs to inactive prodrugs, with a two-fold primary goal- 1. to improve availability of the drug in a target tissue through our novel linker designs and 2. diminishing toxicity by reducing the release of the active drug form our Prodrug in plasma and non-targeted tissues. 

Our various design classes of linkers include those that are 

• – Specifically designed to ferry drug across the blood brain barrier for CNS applications and those that target tissue like lungs, prostate or kidney etc., and also
  
• – Increase availability of drug in diseased tissues
• – Prevent drugs that naturally have high brain exposure from doing so, thereby creating treatment for new indications
• – The linkers are designed to synthesize or conjugate on to them a wide variety of molecules: chemical moieties, oligonucleotides, recombinant proteins and as linker alternatives for whole antibody or antibody fragments

Our payloads consist of

• – Clinician-preferred Drugs with proven efficacy, but often with untenable toxicity or poor bioavailability in the intended tissue
• – New drug candidates generated by our AI platform.

The drug candidates are selected based on patient data along with in vitro and ex vivo analyses, which are being expounded upon with our Tunable Linker Technology- LESS^TM.

PROOF OF CONCEPT

We have shown >30 fold increase in brain penetrance of our LESS-Prodrug as compared to 4%-10% of the original native drug. This opens up a whole new approach to treating CNS disorders like Primary (Glioblastoma) and Metastatic Brain Cancer, Cerebral Edema, Neuro-degenerative diseases like Alzheimer’s, as well as Stroke and Bacterial Encephalitis.

Similarly, we have showed >10 fold greater availability of our prodrugs in lungs with >22 fold reduction in exposure of the active drug in plasma and significantly lower accumulation in skeletal muscles. Some of our linker designs result in bolus effect, while others provide slow release of the active drug. This allows for improved treatment of all inflammatory lung diseases, especially for hard to treat rare diseases like Sarcoidosis.

We have several new drug candidates in early stage of development. More new molecules are being screened using our OncoLib^TM AI screening platform.

 

OncoLib^TM

Our AI platform mines data from over 400 well characterized cancer cell lines (and expanding), 800 known cancer genes and 10⁹ chemical structures to match genomic mutations in diseases and cells with biological outcomes. These Data matches provide insights into appropriate driver pathway of disease. With pathway or target identified, viable chemical structures are determined for in vivo verification. This screening methodology reduces time to lead identification and clinical risk .