# Developing IpY: A novel inhibitor for the treatment of ER+ metastatic breast cancer

> **NIH NIH R43** · CONCARLO HOLDINGS, LLC · 2020 · $320,217

## Abstract

Project Summary/Abstract
The goal of this SBIR is to develop a novel drug, IpY, to improve advanced ER/PR+, Her2- breast cancer
outcomes. Almost 250,000 US women will be diagnosed this year, and over 40,000 will die, suggesting that
despite advances in treatments, breast cancer remains a significant health burden. ER/PR+, Her2- tumors
occur in approximately 40% of breast cancer patients, are associated with poor survival, and are candidates for
estrogen pathway targeting drugs, such as Letrozole, but clinical outcomes for this patient population are still
inadequate: Roughly half of treated ER/PR+ patients will develop metastatic disease within 5 y. CDK4
targeting drugs (CDK4i), like Palbociclib, were recently approved in combination with Letrozole or Fulvestrant
as a frontline therapy for metastatic ER/PR+, Her2- patients. However, even these therapies do not represent
“cure”. While combined ER and CDK4 inhibition treatment significantly extends Progression Free Survival
(PFS), those treated eventually develop resistance to the combination and the Overall Survival (OS) of these
patients is unchanged, suggesting that drug resistance remains an unmet need. Resistance develops because
of compensation by another protein, CDK2, suggesting that to be effective, therapies must be developed to
inhibit BOTH CDK4 and CDK2. The drug, IpY, is a novel peptide-lipid formulation, which targets a different
protein, p27Kip1, that in turn causes inhibition of both CDK4 and CDK2, and represents the first therapeutic
that would accomplish this. IpY reduces proliferation in breast cancer tissue culture models and in vivo,
prevents drug resistance in animal models. IpY is innovative because 1) the p27 target is unique, so blocking it
results in a specific treatment with fewer off-target effects, resulting in less toxicity, 2) IpY targets acquired drug
resistance by hitting both CDK4 and CDK2 at the onset, resulting in a prolonged response to the drug, which
should increase patient survival and 3) IpY can be used alone or in combination with Palbociclib, to make this
already improved therapy better. The hypothesis to be tested in this SBIR project is that IpY can be delivered
efficiently and with limited toxicity in vivo following systemic IV administration to clinically relevant mouse
models, thereby demonstrating the feasibility of using this novel liposomal peptide nanoparticle approach in
more advanced pre-clinical studies. Specifically, this SBIR will 1) demonstrate that IpY reduces tumor
progression and increases OS in genetically engineered models (GEM) that develops breast cancer in
an immunocompetent background, and 2) Demonstrate that IpY has a stable blood half-life and is
delivered to tumors in different models. In Phase II, Concarlo will utilize CROs for the IND-enabling
pharmacokinetics/ADME (absorption, distribution, metabolism, excretion) and Good Laboratory Practice
(GLP)-compliant toxicology studies. Sales of Palbociclib were $1 billion in Q1 2019, b...

## Key facts

- **NIH application ID:** 10008532
- **Project number:** 1R43CA243978-01A1
- **Recipient organization:** CONCARLO HOLDINGS, LLC
- **Principal Investigator:** STACY W BLAIN
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $320,217
- **Award type:** 1
- **Project period:** 2020-07-10 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10008532

## Citation

> US National Institutes of Health, RePORTER application 10008532, Developing IpY: A novel inhibitor for the treatment of ER+ metastatic breast cancer (1R43CA243978-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10008532. Licensed CC0.

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