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Applying high throughput DNA encoded library (DEL) drug screening combined with other advanced technologies in novel ways to deliver small molecule and peptide therapeutics that address some of the most challenging and some previously termed “undruggable” targets in clinical medicine

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TECHNOLOGY

Targeting Kinases

While there are more than 500 kinases encoded within the human genome with over 70 FDA approved small molecule kinase inhibitors, mostly for cancer indications, resistance to first line inhibitors often leads to cancer recurrence and poor prognosis. The development of new drugs that overcome such cancer resistance is still a critical unmet medical need.  Applying DEL technology in novel ways, we screened a library of 7 billion compounds and identified best-in-class new small molecule chemical entities (“NCE”) with single nM IC50s targeting key tyrosine kinases, including ABL1 and its clinically important mutants, including ABL1-T315I, BTK, JAK1/2/3, TYK2, RET, TRKA/B/C, ROS1, AurkA/B/C, SRC and LCK.  We are developing the first “multi kinase inhibitor”, which has single nM IC50 against ABL1-T315I, BTK, AurK, JAK and LCK for patients with Ph+ Acute Lymphocytic Leukemia (“Ph+ ALL”) and Ph+ “Like” ALL.  Our product candidate is up to ~15-fold more effective against some Ph+ ALL patient-derived tumor cell lines than is Iclusig (ponatinib), currently the only approved TKI effective against ABL1-T315I mutants, but that carries a “black box” warning from FDA.

Targeting Nuclear and Other Key Receptors

Nuclear receptors can bind ligand, leading to a conformational change, homo- or hetero-dimerization, nuclear translocation and DNA binding.  Using DEL technologies to screen a proprietary library of stapled peptides, we have identified high affinity binders of the coactivator binding region of the wild type estrogen receptor, ERα, and its mutant, ERα-Y537S.  Having achieved PoC for our proprietary methods of using DEL technology to screen stapled peptide libraries, we are now applying this approach to additional important, difficult to drug targets, including IGF-1 and an immune-regulatory receptor.

Regulating the Senescence-
Associated Secretory Phenotype (SASP)

Cellular senescence is characterized by irreversible cell cycle arrest and a proinflammatory senescence-associated secretory phenotype (SASP), which is a major contributor to aging and age-related diseases.  Senescent cells accumulate during aging and negatively influence lifespan and promote age-dependent changes in several organs.  IL-1, IL-6, IL-8, TNF-α, TGF-β, and various matrix metalloproteinases (MMP3, 12) make up the key components of the SASP.  The sustained inflammatory microenvironment created by the SASP can lead to chronic inflammation, which can have detrimental affects on tissues and organs, contributing to various age-related diseases and conditions.  JAK kinases contribute to the regulation of the SASP through the JAK/STAT pathway.  We are developing “best-in-class” selective JAK2, JAK2/3 and TYK2/JAK3 topical and systemically-delivered TKIs, discovered using our DEL screening technology, as senomorphic therapy, to down-regulate the SASP without the potential negative adverse effects of JAK1 inhibition.

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PIPELINE

Our early pipeline is focused on identifying novel drug candidates, both small molecules or peptides, that target nuclear receptors, senolytics and tyrosine kinases.

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LATEST UPDATES

December 14, 2021 in Press Releases

Rapha Capital BioVentures Fund I Launches DELIVER Therapeutics Inc. with $3 Million Convertible Note Financing

DELIVER Therapeutics, Inc. ("DELIVER") a company that plans to apply novel, high-throughput screening technologies combined with chemical innovation to DELIVER therapeutics that address the most difficult problems in clinical medicine has been launched with an initial $3M Convertible…
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November 15, 2021 in News

New use of screening technology finds SARS-CoV-2 treatment target in lab setting

Finding effective treatments for SARS-CoV-2, the viral agent responsible for COVID-19, has been difficult but researchers at Baylor College of Medicine are working to find a potential solution. Much attention…
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