Company: SHPH
Filing Date: 2025-02-26
Form Type: 10-K
Source: 0001493152-25-008300
Chunk: 17

Company: Shuttle Pharmaceuticals Holdings, Inc.
Filing Date: 2025-02-26
Form: 10-K
Item: Item 1
Chunk 17
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 enhance the immune response in cancer is of great interest. With the introduction
of check-point inhibitors, CAR-T therapies and personalized medicine in cancer, regulation of the immune response to this therapy is
of significant clinical and commercial interest. (See Noonepalle SKR, Grindrod S, Aghdam N, Li X, Gracia-Hernandez M, Zevallos-Delgado
C, Jung M, Villagra A, Dritschilo A. Radiotherapy-induced Immune Response Enhanced by Selective HDAC6 Inhibition. Mol Cancer Ther. 2023
Dec 1;22(12):1376-1389. doi: 10.1158/1535-7163.)

Selective
inhibition of HCAC6 reduces dose limiting side effects associated with non-selective HDAC inhibitors. Selective HDAC6 inhibitors may
be combined with other cytotoxic agents. Shuttle’s discovery of selective HDAC inhibitors has yielded several HDAC6 selective candidate
molecules including SP-2-225. HDAC6 inhibitors are under investigation for roles in the treatment of diseases such as multiple myeloma.

SP-1-303
- Target Indication: Breast Cancer

Histone
deacetylase inhibitors sensitize cancers to the effects of radiation, protect normal tissues from radiation injury and activate the immune
system. SP-1-303 is a selective Class I HDAC inhibitor that inhibits HDAC1, 3 and 6 and has direct cellular toxicity in ER positive breast
cancer cells. Furthermore, SP-1-303 increases the PD-L1 expression level in a time-dependent manner, support combination of SP-1-303
with an immune checkpoint blocker to enhance the therapeutic benefits. We are currently conducting preclinical efficacy studies of these
molecules.

Development
Plan

The
HDAC inhibitor platform of candidate molecules will require pre-clinical evaluation, completion of IND-enabling studies and the lead
drug candidates will be tested in Phase I clinical trials for pharmacokinetics and MTD determination. We have three lead candidates for
potential development for the treatment of solid tumors, including breast cancer, lung cancer and multiple myeloma.

The
results of Phase I and Phase II clinical trials will determine further drug development and Shuttle will seek to establish collaborative
partnerships with other pharmaceutical companies to complete pre-clinical and clinical development, drug manufacturing and marketing
of our product candidates. In the event we are unsuccessful in completing our clinical trials at any