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R42CA265691

Project Grant

Overview

Grant Description
Sirpant Technology for Anti-Cancer Immunity - Project Summary

Immune evasion is a hallmark of cancer. Various tumor immunotherapy treatments, such as immune checkpoint blockade and cancer vaccination, have been developed to overcome cancer's ability to avoid immune detection and destruction; however, the result of these endeavors have not been satisfactory given a number of critical barriers.

One of these barriers, and a prominent mechanism by which cancer evades immune surveillance and elimination, is through the cancer cell expressed CD47 to ligate SIRPA, an ITIMS-containing inhibitory signaling receptor expressed on macrophages, which serves as a negative regulator that inhibits macrophage phagocytosis, proinflammatory response, and antigen presentation.

In our studies, we discovered "Phago-Act" - a proprietary reagent that downregulates SIRPA expression and empowers SIRPA-deficient macrophages (SIRPALOW MØs) to be an initiator for triggering potent innate and adaptive anti-cancer immunity. Not only do they directly phagocytose cancer cells ("liquid"/non-adherent cancer in particular), but SIRPALOW MØs are also capable of conducting immunogenic antigen presentation to robustly activate tumor-specific cytotoxic T cells (TC) with high tumoricidal activities, leading to rapid elimination of late-stage, large-size solid tumors with distal lesions (mimic metastases).

The results of SIRPALOW MØs-initiated responses, which are especially effective in solid tumors, have been vetted extensively in various pre-clinical solid tumor models including cancers of pancreatic, colorectal, lung, breasts, and skin (melanoma), all of which resist advanced anti-cancer therapies including immune checkpoint inhibitors and their combinations with RT and other modalities. Moreover, SIRPALOW MØs-induced tumor elimination also leads to long-lasting anti-cancer immunity that prevents recurrence.

The goal of this fast-track STTR is to leverage these important research findings and to accelerate their translation to clinical implementation of scalable SIRPALOW MØ-based immunotherapy - "Sirpant Technology" - to treat a broad spectrum of cancers and prevent relapse. Our current focus is solid tumors.

In Phase I, we will extend current studies and establish reproducible protocols for producing human SIRPALOW MØ from PBMC (Aim I-1). Phase II is to fund specific IND-enabling CMC refinement (Aim II-1) and toxicology studies (Aim II-2) needed for a Phase I clinical trial, as well as patient applicable SIRPALOW MØs delivery strategies in combined with RT or/and immune checkpoint inhibitors (Aim II-3). (These discoveries and therapeutic developments are protected by our filed patents)
Awardee
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Place of Performance
Chambersburg, Pennsylvania 172028040 United States
Geographic Scope
Single Zip Code
Analysis Notes
Amendment Since initial award the End Date has been extended from 07/31/22 to 07/31/25 and the total obligations have increased 500% from $400,000 to $2,399,999.
Bobcatbio was awarded Project Grant R42CA265691 worth $2,399,999 from National Cancer Institute in September 2021 with work to be completed primarily in Chambersburg Pennsylvania United States. The grant has a duration of 3 years 10 months and was awarded through assistance program 93.395 Cancer Treatment Research. The Project Grant was awarded through grant opportunity PHS 2020-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed).

SBIR Details

Research Type
STTR Phase I
Title
SIRPant Technology for anti-Cancer Immunity
Abstract
PROJECT SUMMARY Immune evasion is a hallmark of cancer. Various tumor immunotherapy treatments, such as immune checkpoint blockade and cancer vaccination, have been developed to overcome cancer’s ability to avoid immune detection and destruction; however, the result of these endeavors have not been satisfactory given a number of critical barriers. One of these barriers, and a prominent mechanism by which cancer evades immune surveillance and elimination, is through the cancer cell expressed CD47 to ligate SIRPα, an ITIMs-containing inhibitory signaling receptor expressed on macrophages, which serves as a negative regulator that inhibits macrophage phagocytosis, proinflammatory response and antigen presentation. In our studies, we discovered “Phago-Act”- a proprietary reagent that downregulates SIRPα expression and empowers SIRPα-deficient macrophages (SIRPαLow MØs) to be an initiator for triggering potent innate and adaptive anti-cancer immunity. Not only do they directly phagocytose cancer cells (“liquid”/non-adherent cancer in particular), but SIRPαLow MØs are also capable of conducting immunogenic antigen presentation to robustly activate tumor-specific cytotoxic T cells (Tc) with high tumoricidal activities, leading to rapid elimination of late-stage, large-size solid tumors with distal lesions (mimic metastases). The results of SIRPαLow MØs-initiated responses, which are especially effective in solid tumors, have been vetted extensively in various pre-clinical solid tumor models including cancers of pancreatic, colorectal, lung, breasts and skin (melanoma), all of which resist advanced anti-cancer therapies including immune checkpoint inhibitors and their combinations with RT and other modalities. Moreover, SIRPαLow MØs- induced tumor elimination also leads to long-lasting anti-cancer immunity that prevents recurrence. The goal of this fast-track STTR is to leverage these important research findings and to accelerate their translation to clinical implement of scalable SIRPαLow MØ-based immunotherapy – “SIRPant Technology” – to treat a broad spectrum of cancers and prevent relapse. Our current focus is Solid Tumors. In Phase I, we will extend current studies and establish reproducible protocols for producing human SIRPαLow MØ from PBMC (Aim I-1). Phase II is to fund specific IND-enabling CMC refinement (Aim II-1) and toxicology studies (Aim II-2) needed for a Phase I clinical trial, as well as patient applicable SIRPαLow MØs delivery strategies in combined with RT or/and immune checkpoint inhibitors (Aim II-3). (These discoveries and therapeutic developments are protected by our filed patents)PROJECT NARRATIVE This project develops a new immunotherapeutic technology that unleashes phagocytes to become key components of defense against cancer, both eliminating tumors and preventing relapse. This technology overcomes immunosuppressive mechanisms that preempts engagement of this potent immune program, and uses phagocytes that are capable of both eating cancer cells and inducing long-lived anti-cancer immune memory.
Topic Code
102
Solicitation Number
PA20-265

Status
(Ongoing)

Last Modified 8/20/24

Period of Performance
9/22/21
Start Date
7/31/25
End Date
99.0% Complete

Funding Split
$2.4M
Federal Obligation
$0.0
Non-Federal Obligation
$2.4M
Total Obligated
100.0% Federal Funding
0.0% Non-Federal Funding

Activity Timeline

Interactive chart of timeline of amendments to R42CA265691

Transaction History

Modifications to R42CA265691

Additional Detail

Award ID FAIN
R42CA265691
SAI Number
R42CA265691-1202813539
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Small Business
Awarding Office
75NC00 NIH NATIONAL CANCER INSTITUTE
Funding Office
75NC00 NIH NATIONAL CANCER INSTITUTE
Awardee UEI
H7HGMZ5YTLQ6
Awardee CAGE
8PDQ9
Performance District
PA-13
Senators
Robert Casey
John Fetterman

Budget Funding

Federal Account Budget Subfunction Object Class Total Percentage
National Cancer Institute, National Institutes of Health, Health and Human Services (075-0849) Health research and training Grants, subsidies, and contributions (41.0) $1,000,000 100%
Modified: 8/20/24