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Overview

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Neoplasms

Respiratory Diseases

Endocrinology and Metabolic Disease

Small molecule drug

Disease domain score

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Technology Platform

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Targets

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Disease Domain	Count

Neoplasms	3
Endocrinology and Metabolic Disease	1

Top 5 Drug Type	Count

Small molecule drug	3

Top 5 Target	Count

GTPase	2
CDK8(Cyclin-dependent kinase 8)	1

AbstractMP1115 is in development as a new immuno-oncology therapeutic lead comprised of bioactive phospholipid containing nanoparticles with activities unique to phospholipid active pharmaceutical ingredients. MP1115 demonstrated potent activation of NK cells in vitro and in vivo and had a secondary anti-tumor cell proliferation mechanism of action. Methods: MP1115 was formulated as ~100 nM diameter nanoparticles formulated in buffered sucrose and stably stored frozen. MP1115 nanoparticles were also loaded with a CDK8 inhibitor test compound at a 30 percent loading efficiency. MP1115 was tested for anti-tumor cell proliferation in 2D and 3D in vitro assays, NK cell activation in ex vivo splenocyte and NK cell activation assays, and anti-tumor efficacy and NK cell activation in vivo in immunocompetent and immunodeficient mice. MP1115-CDK8 inhibitor loaded nanoparticles were tested in vitro for increased anti-tumor cell proliferation compared to non-loaded MP1115 nanoparticles and non-loaded CDK8 inhibitor controls. Results: MP1115 demonstrated increased NK cell activation compared to a CDK8 test compound as measured by IFN-γ release in an ex vivo mouse splenocytes-Yac-1 mouse lymphoma assay (p<0.0001). This activity was maintained with splenocytes from immunocompetent BALB/c mice, immunodeficient BALB/c scid mice, and with purified NK cells from each strain background. MP1115 demonstrated increased NK cell activation of mouse splenocytes in vivo in immunocompetent BALB/c mice compared to controls (p<0.0001), as seen by increased CD69 and CD107a signal, as well as the significant killing of target Yac-1 cells ex vivo (p<0.001). The levels of activation and killing observed were similar to that achieved by a CDK8 inhibitor test compound (p>0.9999). MP1115 also successfully demonstrated the ability to deliver a CDK8 test compound payload to human non-Hodgkin’s lymphoma cells in vitro with increased anti-tumor cell proliferation compared to controls (p<0.0001). MP1115 achieved increased anti-tumor cell proliferation efficacy in acute myeloid leukemia, multiple myeloma, non-Hodgkin’s lymphoma, non-small cell lung cancer, KRAS mutant colorectal cancer models in vitro, and in pancreatic cancer tumor models in vivo. MP1115 demonstrated high tolerability in rodent models when dosed at over 200 mg/kg daily for multiple doses. MP1115 is currently being validated in additional in vivo models including human immune system mice with human xenografts. Conclusions: MP1115 is being advanced to IND-enabling studies based on demonstrated low toxicity, high systemic delivery, potent NK cell activation, and anti-tumor cell proliferation activities.Citation Format: Pitchaimani Kandasamy, Jason E. Duex, Greg Miknis, Julie Lang, Ana Chauca-Diaz, Chris Johnson, Colleen Hudson, Jakub Staszak-Jirkovsky, Neal C. Goodwin. Characterization of MP1115; a new natural killer cell activator [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3949.

1

News (Medical) associated with Machavert Pharmaceuticals LLC

29 Mar 2019

·www.biospace.com

Machavert Pharmaceuticals Will Present at the Annual Meeting of the American Association of Cancer Research (AACR)

A poster presentation reporting Natural Killer cell activation against cancer by a phospholipid molecule and its liposomal formulation MP1115 AURORA, Colo., March 29, 2019 /PRNewswire/ -- Machavert Pharmaceuticals, a preclinical stage pharmaceutical company focused on immuno-oncology and precision medicine cancer therapies, announced today that it will report on the progress of its MP1115 drug candidate at the American Association of Cancer Research (AACR) Annual Meeting 2019 in Atlanta, Georgia. The title of the presentation will be "Characterization of MP1115; a new Natural Killer cell activator" and will be presented as follows: Session Category: Clinical Research Session Title: Immunomodulation by Chemotherapy and Targeted Agents Session Date and Time: Tuesday Apr 2, 2019 1:00 PM - 5:00 PM Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 18 Poster Board Number: 5 Permanent Abstract Number: 3949 The data to be presented at AACR focuses on the recent discovery of phospholipids that activate Natural Killer (NK) cells to trigger anti-tumor cell responses. The phospholipid active pharmaceutical ingredient was formulated as a liposomal nanoparticle, MP1115 that was able to activate NK cells in vitro and in vivo. Preliminary mechanism of action studies revealed downregulation of the CDK8 signaling pathway and pSTAT1-S727. MP1115 showed high tumor bioavailability in vivo and can be combined with payloads to be preferentially delivered to tumors. This was demonstrated in an in vivo orthotopic pancreatic patient derived xenograft tumor model with a fluorescent dye that showed preferential tumor delivery that circumvented liver and other organs. The efficacy of MP1115 monotherapy as well as MP1115 with other payloads is currently being investigated in multiple in-vivo experiments including human immune system tumor models. The drug candidate is currently entering preclinical IND-enabling studies, a prerequisite for seeking FDA IND approval for human clinical trial entry. About Machavert Pharmaceuticals Machavert Pharmaceuticals is a preclinical stage drug development company focused on advanced therapies based on its proprietary bioactive phospholipid platform for the treatment of multiple cancers in hematology and solid tumor oncology. The phospholipid platform is also being combined with other therapeutics such as small molecules for precision medicine and immuno-oncology. Machavert's core focus is on difficult-to-treat driver mutations and other orphan indications in oncology. For further information: Neal Goodwin, Chief Science Officer, Machavert Pharmaceuticals, 720.859.4048, neal.goodwin@machavert.com View original content: SOURCE Machavert Pharmaceuticals

Small molecular drugAACR

100 Deals associated with Machavert Pharmaceuticals LLC

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100 Translational Medicine associated with Machavert Pharmaceuticals LLC

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Pipeline

Pipeline Snapshot as of 26 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

3

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

MP-1115 ( CDK8 )	Solid tumor More	Preclinical
MP-2019 ( GTPase )	Non-Small Cell Lung Cancer More	Preclinical
MP-2018 ( GTPase )	Non-Small Cell Lung Cancer More	Preclinical