Celcuity Inc. operates as a clinical-stage biotechnology company. The company focuses on the development of targeted therapies for the treatment of multiple solid tumor indications.
The company' lead therapeutic candidate is gedatolisib, a potent, well-tolerated, small molecule reversible inhibitor, administered intravenously, that selectively targets all Class I isoforms of phosphatidylinositol-3-kinase (PI3K) and the two mechanistic target of rapamycin (mTOR) sub-complexes, mTORC1 and mTORC2....
Celcuity Inc. operates as a clinical-stage biotechnology company. The company focuses on the development of targeted therapies for the treatment of multiple solid tumor indications.
The company' lead therapeutic candidate is gedatolisib, a potent, well-tolerated, small molecule reversible inhibitor, administered intravenously, that selectively targets all Class I isoforms of phosphatidylinositol-3-kinase (PI3K) and the two mechanistic target of rapamycin (mTOR) sub-complexes, mTORC1 and mTORC2. Gedatolisib's mechanism of action and pharmacokinetic properties are highly differentiated from other approved and investigational therapies that target PI3K or mTOR alone or together.
The company obtained exclusive global development and commercialization rights to gedatolisib in April 2021 under a license agreement with Pfizer, Inc. As of December 31, 2023, 492 patients with solid tumors have received gedatolisib in eight completed clinical trials. Gedatolisib's safety, tolerability and pharmacokinetic profile were determined in a Phase 1 First-in-Human study. Of the 492 patients, 129 were treated with gedatolisib as a single agent in three clinical trials. The remaining 363 patients received gedatolisib in combination with other anti-cancer agents in five clinical trials. Additional patients received gedatolisib in combination with other anti-cancer agents in nine investigator sponsored clinical trials.
The company's initial clinical development programs for gedatolisib are focusing on the treatment of patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), or HR+/HER2-, advanced or metastatic breast cancer and patients with metastatic castration resistant prostate cancer (mCRPC).
In January 2022, gedatolisib was granted Fast Track designation for the treatment of patients with HR+/HER2- metastatic breast cancer after progression on CDK4/6 therapy. Fast Track designation is granted by the U.S. Food and Drug Administration (FDA) for products that are intended for the treatment of serious or life-threatening disease or conditions and which demonstrate the potential to address an unmet medical need.
In July 2022, gedatolisib was granted Breakthrough Therapy Designation for HR+/HER2- advanced breast cancer after progression on CDK4/6 therapy. Breakthrough Therapy designation is granted by the FDA to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition. The criteria for Breakthrough Therapy designation requires preliminary clinical evidence that demonstrates the drug may have substantial improvement on one or more clinically significant endpoints over available therapy.
In December 2022, the company dosed the first patient in its Phase 3, open-label, randomized clinical trial, VIKTORIA-1.
In February 2024, the company dosed its first patient in its Phase 1b/2 clinical trial, CELC-G-201, evaluating gedatolisib in combination with darolutamide in patients with metastatic castration resistant prostate cancer (mCRPC).
Gedatolisib
By targeting multiple nodes of the PAM pathway, gedatolisib can overcome adaptive resistance mechanisms that inhibitors targeting single PI3K/mTOR nodes do not address.
Overcomes limitations of therapies that only inhibit a single Class I PI3K isoform or only one mTOR kinase complex.
Gedatolisib is a pan-class I isoform PI3K inhibitor with low nanomolar potency for the p110alpha, p110beta, p110gamma, and p110delta isoforms. Because gedatolisib inhibits all four PI3K isoforms and both mTOR complexes, it prevents the confounding effect of isoform interaction that may occur with isoform specific PI3K inhibitors and the confounding interaction between PI3K isoforms, AKT, and mTOR. By contrast, node-specific inhibitors cross-activate uninhibited sub-units due to numerous feedforward and feedback loops between the PI3K isoforms, AKT, and mTOR, which in turn induces compensatory resistance that reduces the efficacy of isoform specific PI3K, pan-AKT, or single mTOR kinase complex inhibitors.
To compare the functional effect of inhibiting single versus multiple PAM pathway nodes, the company evaluated gedatolisib, and node-selective inhibitors for PI3Kalpha (alpelisib), AKT (capivasertib) and mTORC1 (everolimus) in a panel of breast cancer cell lines using a live cell proliferation rate dose response analysis.
On average, gedatolisib was 300-fold more potent than the single node PAM inhibitors analyzed and only gedatolisib induced a significant cytotoxic effect. In addition, gedatolisib's potency and efficacy was comparable in cell lines with and without PIK3CA mutations, in contrast to the single node PI3K/protein kinase B (AKT)/mTOR, or PAM inhibitors.
Better tolerated by patients than oral PI3K and mTOR drugs.
Gedatolisib is administered intravenously (IV) on a four-week cycle of three weeks-on, one week-off, in contrast to the orally administered pan-PI3K or dual PI3K/mTOR inhibitors that are no longer being clinically developed.
Clinical Development
As of December 31, 2023, 492 patients with solid tumors have received gedatolisib in eight completed clinical trials. Gedatolisib's safety, tolerability and pharmacokinetic profile were determined in a Phase 1 First-in-Human study. Of the 492 patients, 129 were treated with gedatolisib as a single agent in three clinical trials. The remaining 363 patients received gedatolisib in combination with other anti-cancer agents in five clinical trials. Additional patients received gedatolisib in combination with other anti-cancer agents in nine investigator sponsored clinical trials.
Clinical Experience with Gedatolisib in Breast Cancer
On January 13, 2022, gedatolisib was granted Fast Track designation for the treatment of patients with HR+/HER2- metastatic breast cancer after progression on CDK4/6 therapy. Fast Track designation is granted by the FDA for products that are intended for the treatment of serious or life-threatening disease or conditions and which demonstrate the potential to address an unmet medical need. The designation offers the opportunity for frequent interactions with the FDA to discuss the drug's development plan and to ensure collection of appropriate data needed to support drug approval, as well as eligibility for rolling submission of a New Drug Application.
On July 18, 2022, gedatolisib was granted Breakthrough Therapy Designation for HR+/HER2- advanced breast cancer after progression on CDK4/6 therapy. Breakthrough Therapy designation is granted by the FDA to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition.
Phase 1b HR+/HER2- ABC Clinical Trial Results
A Phase 1b dose-finding trial with an expansion portion for safety and efficacy evaluated gedatolisib when added to either the standard doses of palbociclib plus letrozole or palbociclib plus fulvestrant in patients with HR+/HER2- advanced breast cancer. PI3K mutation status was not used as an eligibility criterion. Patient enrollment for the trial is complete.
A total of 138 patients with HR+/HER2- advanced breast cancer were dosed in the clinical trial. Five patients from this study continue to receive study treatment, as of December 31, 2023, each of whom have received study treatment for more than five years.
Phase 3 HR+/HER2- ABC Clinical Trial (VIKTORIA-1)
In 2022, the company initiated VIKTORIA-1, a Phase 3, open-label, randomized clinical trial to evaluate the efficacy and safety of gedatolisib in combination with fulvestrant with or without palbociclib in adults with HR+/HER2- advanced breast cancer whose disease has progressed after prior CDK4/6 therapy in combination with an aromatase inhibitor. This multi-center, international trial is expected to enroll approximately 701 total subjects at more than 200 clinical sites across North America, Europe, Latin America, and Asia. The first patient was dosed in December 2022.
Prostate Cancer Program
Phase 1b/2 mCRPC Clinical Trial (CELC-G-201)
The company received approval from the U.S. FDA in mid-2023 to proceed with the clinical development of gedatolisib in combination with Nubeqa (darolutamide), an approved androgen receptor inhibitor, for the treatment of patients with mCRPC. The company has since initiated a Phase 1b/2 study (CELC-G-201) that will enroll up to 54 participants with mCRPC who progressed after treatment with an androgen receptor inhibitor. The company dosed its first patient in this trial in February 2024.
Pfizer License Agreement
In April 2021, the company entered into a license agreement, or the Gedatolisib License Agreement, with Pfizer pursuant to which it acquired exclusive (including as to Pfizer) worldwide sublicensable rights to research, develop, manufacture, and commercialize gedatolisib for the treatment, diagnosis and prevention of all diseases. Pursuant to the Gedatolisib License Agreement, the company is obligated to use commercially reasonable efforts to develop and seek regulatory approval for at least one product in the U.S. and if regulatory approval is obtained, to commercialize such product in the U.S and at least one international major market.
Sales and Marketing
If any of its product candidates are approved, the company intends to market and commercialize them in the U.S. and select international markets, either alone or in partnership with others.
CELsignia
The company founded its company to develop its proprietary CELsignia diagnostic platform and relied on the capability of this technology to identify its lead drug candidate, gedatolisib. CELsignia characterizes the specific activity of various oncogenic signaling pathways, including the PAM pathway, in living patient tumor cells.
The company is supporting the advancement of new potential indications for three different targeted therapies, controlled by other pharmaceutical companies, that would rely on a CELsignia companion diagnostic test to select patients. The company's first analytically validated and commercially ready test using its CELsignia platform, the CELsignia HER2 Pathway Activity Test for breast cancer, diagnoses two new sub-types of HER2-negative breast cancer that traditional molecular diagnostics cannot detect. The company's internal studies show that approximately 15-20% of HER2-negative breast cancer patients have abnormal HER2 signaling activity similar to levels found in HER2-positive breast cancer cells. As a result, these HER2-negative patients have undiagnosed HER2-driven breast cancer and would be likely to respond to the same anti-HER2 targeted therapies only HER2-positive patients receive today. The company has two interventional clinical trials underway to evaluate the efficacy of HER2 targeted therapies in breast cancer patients selected with our CELsignia HER2 Pathway Activity Test.
The company's second CELsignia test for breast cancer evaluates independent c-Met signaling activity and its involvement with HER family signaling in HER2-negative breast cancer tumor cells. The company's internal studies show that approximately 20%-25% of HER2-negative breast cancer patients have abnormal c-Met signaling activity that is co-activated with abnormal HER family signaling. These studies suggest that this sub-group of HER2-negative breast cancer patients may best respond to treatment with a combination of HER family and c-Met inhibitors. The company has one interventional clinical trial underway to evaluate the efficacy of HER2 and c-Met targeted therapies, in previously treated metastatic HER2-negative breast cancer patients selected with its CELsignia Multi-Pathway Activity Test, or CELsignia MP Test.
The company's third CELsignia test for breast cancer evaluates PI3K signaling in HER2-negative breast cancer tumor cells.
CELsignia Clinical Trials
The company is collaborating on three Phase 2 clinical trials to evaluate the efficacy of its collaboration partners' targeted therapies in patients selected with one of the company's CELsignia tests. The goal of these trials is to support the development of three potential new drug indications to treat patient groups found responsive by the company's CELsignia test to their approved targeted therapies. These clinical trials include:
FACT-1 Clinical Trial to Evaluate Efficacy of Genentech's HER2 Targeted Therapies. The company is collaborating with NSABP Foundation, Inc. (NSABP) and Genentech, Inc. (Genentech) to evaluate the efficacy and safety of Genentech's drugs, Herceptin (trastuzumab) and Perjeta (pertuzumab), and chemotherapy in breast cancer patients selected with the company's CELsignia test. The goal is to demonstrate that patients who have an abnormal HER2 signaling pathway, as identified by the company's CELsignia test, respond to treatment with a matching targeted therapy.
FACT-5 Clinical Trial to Evaluate Efficacy of Puma's pan-HER Inhibitor and chemotherapy. The company is collaborating with University of Rochester Wilmot Cancer Center and Puma to evaluate the efficacy and safety of Puma's drug, Nerlynx (neratinib), and the chemotherapy capecitabine, in previously treated metastatic HER2-negative breast cancer patients with brain metastases selected with the company's CELsignia HER2 Pathway Activity Test. The goal of the trial is to demonstrate that previously treated HER2-negative metastatic breast cancer patients with brain metastases who have hyperactive HER2 signaling tumors, as identified by the CELsignia test, respond to treatment with Nerlynx in combination with capecitabine.
FACT-6 Clinical Trial to Evaluate Efficacy of Novartis's c-Met Inhibitor and Puma's pan-HER Inhibitor. The company is collaborating with MD Anderson Cancer Center, Novartis AG, and Puma, to conduct a Phase 1/2 clinical trial. This open-label Phase 1/2 trial will evaluate the efficacy and safety of Novartis' c-Met inhibitor, Tabrecta (capmatinib), and Puma's pan-HER inhibitor, Nerlynx (neratinib), in previously treated metastatic HER2-negative breast cancer patients selected with the company's CELsignia MP Test. The goal of the trial is to demonstrate that previously treated HER2-negative metastatic breast cancer patients who have hyperactive HER2 and c-Met signaling tumors, as identified by the CELsignia test, respond to treatment with Tabrecta in combination with Nerlynx.
Principal Suppliers for CELsignia
The company's principal reagent suppliers include Bio-Techne Corporation, Selleck Chemicals, Sigma-Aldrich, and VWR International. The company's principal instrument suppliers include Agilent Technologies, Integra Biosciences, Invitrogen, and Thermo Fisher Scientific.
Intellectual Property
Gedatolisib Patents
The company entered into the Gedatolisib License Agreement with Pfizer in April 2021, pursuant to which it acquired exclusive worldwide rights under Pfizer patents and know-how to develop, manufacture and commercialize gedatolisib. The company has exclusive licenses under the Gedatolisib License Agreement to patent rights in the U.S. and numerous foreign jurisdictions relating to gedatolisib. The patent rights in-licensed under the Gedatolisib License Agreement include 11 granted patents in the U.S. and more than 290 patents granted in foreign jurisdictions including Australia, Canada, China, France, Germany, Spain, United Kingdom and Japan. The U.S. patents covering gedatolisib as a composition of matter have a statutory expiration date in May 2029. A U.S. composition of matter patent that covers the lactic acid form of gedatolisib expires in December 2035. A pending U.S. application covering the cyclodextrin formulation of gedatolisib that is in clinical development expires in June 2039, in each case, not including patent term adjustment or any patent term extension, and relevant foreign counterparts.
CELsignia Patents
With respect to CELsignia, the company has seven issued U.S. patents and more than 30 issued international patents covering its diagnostic approach using cell signaling analysis in living patient cells to guide treatment of patients with targeted therapies and cell sample preparation methods. The earliest expiration date of the patents is 2032. In addition, the company has developed significant proprietary know-how and trade secrets for the various cell sample preparation and cellular analysis methods it has developed.
Government Regulation
The company's CELsignia tests are laboratory developed tests, or LDTs, and subject to regulation under the Clinical Laboratory Improvement Amendments, or CLIA. The company received its CLIA certification in 2016. The company also had its laboratory certified by the College of American Pathologies, or CAP, in 2016, an organization recognized by CMS as a third-party reviewer of clinical laboratories.
Research and Development
The company's research and development costs amounted to $60,594,005 for the year ended December 31, 2023.
History
The company was founded in 2011 and commenced operations in 2012. It was incorporated in 2017. In 2017, the company changed its name from Celcuity LLC to Celcuity Inc.
