G1 Therapeutics, Inc. is an American

biopharmaceutical A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, t ...

company headquartered in

Research Triangle Park Research Triangle Park (RTP) is the largest research park in the United States, occupying in North Carolina and hosting more than 300 companies and 65,000 workers. The facility is named for its location relative to the three surrounding cities ...

North Carolina North Carolina () is a state in the Southeastern region of the United States. The state is the 28th largest and 9th-most populous of the United States. It is bordered by Virginia to the north, the Atlantic Ocean to the east, Georgia and So ...

. The company specializes in developing and commercializing small molecule therapeutics for the treatment of patients with cancer.

History

G1 Therapeutics was co-founded in 2008 by

Norman Sharpless Norman Edward "Ned" Sharpless (born September 20, 1966) is the previous Director of the National Cancer Institute (NCI). Before that, Sharpless was Professor of Medicine and Genetics Chair, Director of University of North Carolina UNC Lineberger ...

, 15th Director of the

National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...

, and Kwok-Kin Wong, to develop and commercialize drug candidates discovered at, and licensed from, Sharpless’ lab at the

University of North Carolina at Chapel Hill A university () is an institution of higher (or tertiary) education and research which awards academic degrees in several academic disciplines. Universities typically offer both undergraduate and postgraduate programs. In the United States ...

. Early investors in G1 included Hatteras Venture Partners, and Fred Eshelman, founder of

PPD, Inc. Pharmaceutical Product Development (PPD) is a global contract research organization (CRO) providing comprehensive, integrated drug development, laboratory and lifecycle management services. In December 2021, PPD became a wholly owned subsidiary ...

Other early investors included AstraZeneca’s venture capital fund MedImmune Ventures, and Cormorant Asset Management. G1 went public on May 17, 2017 and trades on the

NASDAQ The Nasdaq Stock Market () (National Association of Securities Dealers Automated Quotations Stock Market) is an American stock exchange based in New York City. It is the most active stock trading venue in the US by volume, and ranked second ...

under the ticker symbol GTHX. On September 30, 2020, the company announced CEO, Mark Velleca, will be stepping down on January 1, 2021, and is to be replaced by Jack Bailey, former President of U.S. pharmaceuticals and vaccines for

GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the ten ...

Pipeline

Trilaciclib – G1T28

Trilaciclib Trilaciclib, sold under the brand name Cosela, is a medication used to reduce the frequency of chemotherapy-induced bone marrow suppression. The most common side effects include fatigue; low levels of calcium, potassium and phosphate; increase ...

, a

small molecule Within the fields of molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs ar ...

CDK4/6 inhibitor, is a first-in-class, FDA-designated

Breakthrough therapy Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "br ...

designed to improve outcomes for cancer patients being treated with

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

. The drug's first targeted indication is

small cell lung cancer Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell car ...

( SCLC). Patients receiving chemotherapy as part of SCLC treatment frequently experience chemotherapy-induced myelosuppression. In three randomized, placebo-controlled SCLC trials,

trilaciclib Trilaciclib, sold under the brand name Cosela, is a medication used to reduce the frequency of chemotherapy-induced bone marrow suppression. The most common side effects include fatigue; low levels of calcium, potassium and phosphate; increase ...

, when administered to patients before

, significantly reduced the occurrence of chemotherapy-induced myelosuppression and the need for supportive care. In June 2020, G1 filed a New Drug Application (NDA) with the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...

). The application was granted

Priority Review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

with a

Prescription Drug User Fee Act The ''Prescription Drug User Fee Act'' (PDUFA) was a law passed by the United States Congress in 1992 which allowed the Food and Drug Administration (FDA) to collect fees from Pharmaceutical company, drug manufacturers to fund the new medication, ...

(PDUFA) date set for February 15, 2021. In September 2020, G1 launched an

expanded access Expanded access or compassionate use is the use of an unapproved drug or medical device under special forms of investigational new drug applications (IND) or IDE application for devices, outside of a clinical trial, by people with serious or life ...

program providing SCLC patients access to

while the drug is under

review. The

approved

for use in SCLC on February 12, 2021. In March 2021,

was added to the

National Comprehensive Cancer Network National Comprehensive Cancer Network (NCCN) is an alliance of 32 cancer centers in the United States, most of which are designated by the National Cancer Institute (one of the U.S. National Institutes of Health) as comprehensive cancer centers. It ...

(NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) as an appropriate

prophylactic Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...

option to decrease the incidence of chemotherapy-induced

myelosuppression Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (t ...

for patients undergoing

for extensive-stage

small-cell lung cancer Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell car ...

is one of several novel agents under review for

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

treatment as part of the I-SPY series of clinical trials organized by Quantum Leap Healthcare Collaborative. In October 2020, G1 initiated a Phase 3 registrational study (NCT04607668 - PRESERVE 1) evaluating the impact of

on myelopreservation and antitumor efficacy in patients receiving

for metastatic

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...

. In March 2021, the company initiated a Phase 3 registrational study (NCT04799249 - PRESERVE 2) evaluating

in patients receiving first- or second-line

gemcitabine Gemcitabine, with brand names including Gemzar, is a chemotherapy medication. It treats cancers including testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder cancer. It is administered by i ...

and

carboplatin Carboplatin, sold under the trade name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is used b ...

for locally advanced, unresectable, or

metastatic Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

triple-negative breast cancer Triple-negative breast cancer (TNBC) is any breast cancer that lacks or show low levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) overexpression and/or gene amplification (i.e. the tum ...

. In April 2021, G1 initiated a Phase 2 study (NCT04863248 – PRESERVE 4) evaluating

in patients with

non-small cell lung cancer Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to sm ...

who are receiving the

agent

docetaxel Docetaxel (DTX or DXL), sold under the brand name Taxotere among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer, head and neck cancer, stomach cancer, prostate cancer and non-small-ce ...

. In May 2021, G1 initiated a Phase 2 study (NCT04887831 – PRESERVE 3) evaluating

in patients with

bladder cancer Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become mali ...

who are receiving

followed by

avelumab Avelumab, sold under the brand name Bavencio, is a fully human monoclonal antibody medication for the treatment of Merkel cell carcinoma, urothelial carcinoma, and renal cell carcinoma. Common side effects include fatigue, musculoskeletal pain, ...

Rintodestrant – G1T48

Rintodestrant, an oral

selective estrogen receptor degrader A selective estrogen receptor degrader or downregulator (SERD) is a type of drug which binds to the estrogen receptor (ER) and, in the process of doing so, causes the ER to be degraded and thus downregulated. They are used to treat estrogen recep ...

( SERD), is being developed as a treatment for ER-Positive, HER2-Negative advanced

, both as monotherapy and in

combination In mathematics, a combination is a selection of items from a set that has distinct members, such that the order of selection does not matter (unlike permutations). For example, given three fruits, say an apple, an orange and a pear, there are th ...

with

palbociclib Palbociclib, sold under the brand name Ibrance among others, is a medication developed by Pfizer for the treatment of HR-positive and HER2-negative breast cancer. It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. Pal ...

, a CDK 4/6 inhibitor marketed by

Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...

as Ibrance.

Lerociclib – G1T38

Lerociclib is a potent, selective oral CDK4/6 inhibitor. Preclinical and early clinical data have demonstrated that lerociclib is differentiated from other CDK4/6 inhibitors based on its favorable safety profile and ability to be dosed continuously with less dose-limiting

neutropenia Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria ...

Products

Cosela Trilaciclib, sold under the brand name Cosela, is a medication used to reduce the frequency of chemotherapy-induced bone marrow suppression. The most common side effects include fatigue; low levels of calcium, potassium and phosphate; increase ...

: On February 12, 2021, the

approved

(brand name

) as a treatment to reduce the frequency of chemotherapy-induced

for patients receiving certain types of

for extensive-stage

Collaborations

* In June 2020, G1 entered into a commercialization agreement with

Boehringer Ingelheim C.H. Boehringer Sohn AG & Co. is the parent company of the Boehringer Ingelheim group, which was founded in 1885 by Albert Boehringer in Ingelheim am Rhein, Germany. As of 2018, Boehringer Ingelheim is one of the world's largest pharmaceutical ...

to co-promote trilaciclib for SCLC in the United States and Puerto Rico. * In August 2020, Simcere Pharmaceuticals licensed the development and commercialization rights to trilaciclib for greater China. * G1 has a non-exclusive clinical supply agreement with

to provide

for its rintodestrant/palbociclib breast cancer trial. * In July 2020, G1 entered into a licensing agreement for lerociclib with EQRx. The license provides exclusive rights to develop the drug for the USA, Europe, Japan, and other global markets, excluding the Asia-Pacific region (except Japan). * In June 2020, G1 licensed the rights to develop lerociclib in the Asia-Pacific region to Genor Biopharma. *In August 2020, G1 licensed the rights to its preclinical CDK2 inhibitor program to ARC Therapeutics.

Footnotes

* Tan, A.R. et al., November 2019, ''Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer: a multicentre, randomised, open-label, phase 2 trial'', The Lancet, Oncology, Volume 20, Issue11, Pages 1587-1601. * Weiss, J.M., et al., October 1, 2019, ''Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial''. Annals of Oncology, 30(10), Pages 1613-1621. * Davey, D., et al., December 21, 2020, ''Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer: a multicentre, randomised, double-blind, placebo-controlled phase II trial'', International Journal of Cancer, DOI
10.1002/ijc.33453
* Hart, L., et al., ''Myelopreservation with Trilaciclib in Patients Receiving Topotecan for Small Cell Lung Cancer. Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Study'', Advances in Therapy, 29 October 2020, DOI
10.1007/s12325-020-01538-0
* Sorrentino, J. A., et al., July 2017, ''Trilaciclib (G1T28), a CDK4/6 inhibitor, enhances the efficacy of combination chemotherapy and immune checkpoint inhibitor treatment in preclinical models'', American Association for Cancer Research, 2017 Proceedings. * He, S. et al., April 26, 2017, ''Transient CDK4/6 inhibition protects hematopoietic stem cells from chemotherapy-induced exhaustion'', Science Translational Medicine
DOI: 10.1126/scitranslmed.aal3986
* Lai, A. Y., et al., October 1, 2020, ''CDK4/6 inhibition enhances antitumor efficacy of chemotherapy and immune checkpoint inhibitor combinations in preclinical models and enhances T-cell activation in patients with SCLC receiving chemotherapy,'' Journal for Immunotherapy of Cancer, DOI
10.1136/jitc-2020-000847
* Chabner, B. A., Longo, D. L., 2018, ''Cancer Chemotherapy, Immunotherapy and Biotherapy: Principles and Practice'', 6th Ed. Lippincott Williams & Wilkins (LWW).

References

{{reflist

External Links

Official website

G1 Corporate Presentation
* Business data for G1 Therapeutics
Yahoo FinanceNasdaqReutersSEC filings
*G1 Therapeutics o
clinicaltrials.govCosela
Companies based in North Carolina Biopharmaceutical companies Biotechnology companies of the United States