G1 Therapeutics

Last updated

G1 Therapeutics
Company typePublic
Nasdaq:  GTHX
Industry Pharmaceuticals
Founded2008;16 years ago (2008)
Founders Norman Sharpless
Headquarters North Carolina, United States
Key people
Jack Bailey, CEO

Terry Murdock, COO

John Umstead V, CFO

Raj Malik, M.D., CMO

Andrew Perry, CCO

Mark Avagliano, CBO
Products Cosela
Number of employees
170 (Dec. 2022)
Website g1therapeutics.com

G1 Therapeutics, Inc. is an American biopharmaceutical company headquartered in Research Triangle Park, North Carolina. The company specializes in developing and commercializing small molecule therapeutics for the treatment of patients with cancer. [1]

Contents

History

G1 Therapeutics was co-founded in 2008 by Norman Sharpless, 15th Director of the National Cancer Institute, 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. [2] Early investors in G1 included Hatteras Venture Partners, and Fred Eshelman, founder of PPD, Inc. [3] Other early investors included AstraZeneca’s venture capital fund MedImmune Ventures, and Cormorant Asset Management. [4]

G1 went public on May 17, 2017 and trades on the NASDAQ under the ticker symbol GTHX. [5] 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. [6]

Pipeline

Trilaciclib – G1T28

Trilaciclib, a small molecule CDK4/6 inhibitor, is a first-in-class, FDA-designated Breakthrough therapy designed to improve outcomes for cancer patients being treated with chemotherapy. [7] The drug's first targeted indication is small cell lung cancer (SCLC). [8] Patients receiving chemotherapy as part of SCLC treatment frequently experience chemotherapy-induced myelosuppression. [9] In three randomized, placebo-controlled SCLC trials, trilaciclib, when administered to patients before chemotherapy, significantly reduced the occurrence of chemotherapy-induced myelosuppression and the need for supportive care. [10] In June 2020, G1 filed a New Drug Application (NDA) with the Food and Drug Administration (FDA). [11] The application was granted Priority Review with a Prescription Drug User Fee Act (PDUFA) date set for February 15, 2021. [12] In September 2020, G1 launched an expanded access program providing SCLC patients access to trilaciclib while the drug is under FDA review. [13] The FDA approved trilaciclib for use in SCLC on February 12, 2021. [14] In March 2021, trilaciclib was added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) as an appropriate prophylactic option to decrease the incidence of chemotherapy-induced myelosuppression for patients undergoing chemotherapy for extensive-stage small-cell lung cancer. [15]

Trilaciclib is one of several novel agents under review for breast cancer treatment as part of the I-SPY series of clinical trials organized by Quantum Leap Healthcare Collaborative. [16]

In October 2020, G1 initiated a Phase 3 registrational study (NCT04607668 - PRESERVE 1) [17] evaluating the impact of trilaciclib on myelopreservation and antitumor efficacy in patients receiving chemotherapy for metastatic colorectal cancer. [18] In March 2021, the company initiated a Phase 3 registrational study (NCT04799249 - PRESERVE 2) evaluating trilaciclib in patients receiving first- or second-line gemcitabine and carboplatin chemotherapy for locally advanced, unresectable, or metastatic triple-negative breast cancer. [19] In April 2021, G1 initiated a Phase 2 study (NCT04863248 – PRESERVE 4) evaluating trilaciclib in patients with metastatic non-small cell lung cancer who are receiving the chemotherapy agent docetaxel. [20] In May 2021, G1 initiated a Phase 2 study (NCT04887831 – PRESERVE 3) evaluating trilaciclib in patients with metastatic bladder cancer who are receiving chemotherapy followed by avelumab. [21]

Rintodestrant – G1T48

Rintodestrant, an oral selective estrogen receptor degrader (SERD), is being developed as a treatment for ER-Positive, HER2-Negative advanced breast cancer, both as monotherapy and in combination with palbociclib, a CDK 4/6 inhibitor marketed by Pfizer as Ibrance. [22] [23] [24]

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. [25]

Products

Cosela: On February 12, 2021, the FDA approved trilaciclib (brand name Cosela) as a treatment to reduce the frequency of chemotherapy-induced myelosuppression for patients receiving certain types of chemotherapy for extensive-stage small-cell lung cancer. [26]

Collaborations

Footnotes

Related Research Articles

<span class="mw-page-title-main">Small-cell carcinoma</span> Type of malignant 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 carcinoma, small cell carcinoma is more aggressive, with a shorter doubling time, higher growth fraction, and earlier development of metastases.

<span class="mw-page-title-main">Pemetrexed</span> Chemical compound

Pemetrexed, sold under the brand name Alimta among others, is a chemotherapy medication for the treatment of pleural mesothelioma and non-small cell lung cancer (NSCLC).

Bevacizumab, sold under the brand name Avastin among others, is a monoclonal antibody medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, lung cancer, ovarian cancer, glioblastoma, hepatocellular carcinoma, and renal-cell carcinoma. In many of these diseases it is used as a first-line therapy. For age-related macular degeneration it is given by injection into the eye (intravitreal).

<span class="mw-page-title-main">Targeted therapy</span> Type of therapy

Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells. Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy. However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.

<span class="mw-page-title-main">Sunitinib</span> Cancer medication

Sunitinib, sold under the brand name Sutent, is an anti-cancer medication. It is a small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) in January 2006. Sunitinib was the first cancer drug simultaneously approved for two different indications.

Ramucirumab, sold under the brand name Cyramza, is a fully human monoclonal antibody (IgG1) used for the treatment of cancer. Ramucirumab is a human vascular endothelial growth factor receptor 2 (VEGFR2) antagonist. Ramucirumab was developed by ImClone Systems. It was isolated from a native phage display library from Dyax.

Spectrum Pharmaceuticals, Inc. is an American biopharmaceutical company located in Boston, MA. It develops and markets drugs for treatments in hematology and oncology.

<span class="mw-page-title-main">Olaparib</span> Chemical compound (cancer therapy drug)

Olaparib, sold under the brand name Lynparza, is a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair. It acts against cancers in people with hereditary BRCA1 or BRCA2 mutations, which include some ovarian, breast, and prostate cancers.

<span class="mw-page-title-main">Phosphoinositide 3-kinase inhibitor</span>

Phosphoinositide 3-kinase inhibitors are a class of medical drugs that are mainly used to treat advanced cancers. They function by inhibiting one or more of the phosphoinositide 3-kinase (PI3K) enzymes, which are part of the PI3K/AKT/mTOR pathway. This signal pathway regulates cellular functions such as growth and survival. It is strictly regulated in healthy cells, but is always active in many cancer cells, allowing the cancer cells to better survive and multiply. PI3K inhibitors block the PI3K/AKT/mTOR pathway and thus slow down cancer growth. They are examples of a targeted therapy. While PI3K inhibitors are an effective treatment, they can have very severe side effects and are therefore only used if other treatments have failed or are not suitable.

A CDK inhibitor is any chemical that inhibits the function of CDKs. They are used to treat cancers by preventing overproliferation of cancer cells. The US FDA approved the first drug of this type, palbociclib (Ibrance), a CDK4/6 inhibitor, in February 2015, for use in postmenopausal women with breast cancer that is estrogen receptor positive and HER2 negative. While there are multiple cyclin/CDK complexes regulating the cell cycle, CDK inhibitors targeting CDK4/6 have been the most successful; four CDK4/6 inhibitors have been FDA approved. No inhibitors targeting other CDKs have been FDA approved, but several compounds are in clinical trials.

Treatment of lung cancer refers to the use of medical therapies, such as surgery, radiation, chemotherapy, immunotherapy, percutaneous ablation, and palliative care, alone or in combination, in an attempt to cure or lessen the adverse impact of malignant neoplasms originating in lung tissue.

<span class="mw-page-title-main">Pembrolizumab</span> Pharmaceutical drug used in cancer treatment

Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody, more specifically a PD-1 Inhibitor, used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer. It is administered by slow intravenous injection.

<span class="mw-page-title-main">Palbociclib</span> Medication for HR+ HER2− breast cancer

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. Palbociclib was the first CDK4/6 inhibitor to be approved as a cancer therapy.

<span class="mw-page-title-main">Durvalumab</span> Pharmaceutical drug

Durvalumab, sold under the brand name Imfinzi, is an FDA-approved immunotherapy for cancer, developed by Medimmune/AstraZeneca. It is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that blocks the interaction of programmed cell death ligand 1 (PD-L1) with the PD-1 (CD279).

<span class="mw-page-title-main">Atezolizumab</span> Monoclonal anti-PD-L1 antibody

Atezolizumab, sold under the brand name Tecentriq among others, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma and alveolar soft part sarcoma, but discontinued for use in triple-negative breast cancer (TNBC). It is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1).

A selective estrogen receptor degrader or downregulator (SERD) is a type of drug that selectively binds to the estrogen receptor (ER) and induces its degradation, and thus causes its downregulation. SERDs are used in the treatment of estrogen receptor-positive breast cancer, particularly in cases where tumors have developed resistance to other forms of endocrine therapy, such as selective estrogen receptor modulators (SERMs) or aromatase inhibitors.

<span class="mw-page-title-main">Abemaciclib</span> Anti-breast cancer medication

Abemaciclib, sold under the brand name Verzenio among others, is a medication for the treatment of advanced or metastatic breast cancers. It was developed by Eli Lilly and it acts as a CDK inhibitor selective for CDK4 and CDK6.

<span class="mw-page-title-main">Tucatinib</span> Chemical compound

Tucatinib, sold under the brand name Tukysa, is an anticancer medication used for the treatment of HER2-positive breast cancer. It is a small molecule inhibitor of HER2. It was developed by Array BioPharma and licensed to Cascadian Therapeutics.

<span class="mw-page-title-main">Trilaciclib</span> Chemical compound

Trilaciclib, sold under the brand name Cosela, is a medication used to reduce the frequency of chemotherapy-induced bone marrow suppression.

<span class="mw-page-title-main">Lurbinectedin</span> Chemical compound

Lurbinectedin, sold under the brand name Zepzelca, is a medication used for the treatment of small cell lung cancer.

References

  1. Kaplan S (12 March 2019). "National Cancer Chief, Ned Sharpless, Named F.D.A.'s Acting Commissioner (Published 2019)". The New York Times. ISSN   0362-4331 . Retrieved 11 December 2020.
  2. McGinley L, Goldstein A. "Nation's cancer chief appointed acting FDA commissioner". Washington Post. ISSN   0190-8286 . Retrieved 11 December 2020.
  3. "UNC spinout gets $33M for cancer treatment". www.bizjournals.com. Retrieved 11 December 2020.
  4. "SEC Filing - G1 Therapeutics, Inc". investor.g1therapeutics.com. Retrieved 11 December 2020.
  5. "Xconomy: Cancer Drugmaker G1 Therapeutics Makes IPO Pitch To Wall Street". Xconomy. 17 April 2017. Retrieved 11 December 2020.
  6. "G1 Therapeutics CEO Mark Vellecca to Step Down". Citybizlist. Retrieved 7 January 2021.
  7. "Trilaciclib | intravenous CDK4/6 inhibitor | G1 Therapeutics, Inc". www.g1therapeutics.com. Retrieved 10 January 2021.
  8. "FDA Grants Priority Review to Trilaciclib in Small Cell Lung Cancer". Targeted Oncology. Retrieved 5 January 2021.
  9. Epstein, Robert S.; Krenitsky, JoAnn; Weerasinghe, Roshanthi K.; Parrish, Amy S.; Sanborn, Rachel E.; Salimi, Tehseen (20 May 2020). "Real-world burden of myelosuppression in patients with small cell lung cancer (SCLC): Retrospective, longitudinal data analysis" . Journal of Clinical Oncology. 38 (15_suppl): e19300. doi:10.1200/JCO.2020.38.15_suppl.e19300. ISSN   0732-183X. S2CID   219774668.
  10. Weiss, Jared; Goldschmidt, Jerome; Zoran, Andric; Dragnev, Konstantin H.; Pritchett, Yili; Morris, Shannon R.; Malik, Rajesh K.; Daniel, Davey B. (20 May 2020). "Myelopreservation and reduced use of supportive care with trilaciclib in patients with small cell lung cancer". Journal of Clinical Oncology. 38 (15_suppl): 12096. doi:10.1200/JCO.2020.38.15_suppl.12096. ISSN   0732-183X. S2CID   219780224.
  11. "FDA Grants Trilaciclib Priority Review for Small Cell Lung Cancer". OncLive. Retrieved 11 December 2020.
  12. "FDA Grants Priority Review to Trilaciclib to Treat Patients with SCLC". Cancer Network. Retrieved 11 December 2020.
  13. "FDA Grants Priority Review to Trilaciclib in Small Cell Lung Cancer". Targeted Oncology. Retrieved 11 December 2020.
  14. "FDA Approves Cosela (trilaciclib) to Decrease the Incidence of Chemotherapy-Induced Myelosuppression". Drugs.com. Retrieved 17 February 2021.
  15. "NCCN Clinical Practice Guidelines in Oncology". www.nccn.org. Retrieved 25 March 2021.
  16. "The I-SPY Trials". www.ispytrials.org. Retrieved 18 February 2021.
  17. G1 Therapeutics, Inc. (13 January 2021). "PRESERVE 1: A Phase 3 Randomized, Double-blind Trial of Trilaciclib Versus Placebo in Patients Receiving FOLFOXIRI/Bevacizumab for Metastatic Colorectal Cancer".{{cite journal}}: Cite journal requires |journal= (help)CS1 maint: numeric names: authors list (link)
  18. G1 Therapeutics, Inc. (10 December 2020). "PRESERVE 1: A Phase 3 Randomized, Double-blind Trial of Trilaciclib Versus Placebo in Patients Receiving FOLFOXIRI/Bevacizumab for Metastatic Colorectal Cancer".{{cite journal}}: Cite journal requires |journal= (help)CS1 maint: numeric names: authors list (link)
  19. G1 Therapeutics, Inc. (11 March 2021). "A Phase 3, Randomized, Double-Blind Study of Trilaciclib or Placebo in Patients Receiving First- or Second-Line Gemcitabine and Carboplatin Chemotherapy for Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer (PRESERVE 2)".{{cite journal}}: Cite journal requires |journal= (help)CS1 maint: numeric names: authors list (link)
  20. G1 Therapeutics, Inc. (23 April 2021). "A Phase 2 Randomized, Double-blind, Clinical Trial of Trilaciclib Versus Placebo in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC) Treated With Docetaxel in the 2nd/3rd Line Setting (PRESERVE 4)".{{cite journal}}: Cite journal requires |journal= (help)CS1 maint: numeric names: authors list (link)
  21. G1 Therapeutics, Inc. (13 May 2021). "A Phase 2, Randomized, Open-Label Study of Trilaciclib Administered With First-Line Platinum-Based Chemotherapy and Avelumab Maintenance Therapy in Patients With Untreated, Locally Advanced or Metastatic Urothelial Carcinoma (PRESERVE 3)".{{cite journal}}: Cite journal requires |journal= (help)CS1 maint: numeric names: authors list (link)
  22. G1 Therapeutics, Inc. (16 September 2020). "A Phase 1, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Ascending Doses of G1T48 Alone and in Combination With Palbociclib in Women With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer".{{cite journal}}: Cite journal requires |journal= (help)CS1 maint: numeric names: authors list (link)
  23. "Rintodestrant - G1 Therapeutics - AdisInsight". adisinsight.springer.com. Retrieved 11 December 2020.
  24. Andreano KJ, Wardell SE, Baker JG, Desautels TK, Baldi R, Chao CA, et al. (April 2020). "G1T48, an oral selective estrogen receptor degrader, and the CDK4/6 inhibitor lerociclib inhibit tumor growth in animal models of endocrine-resistant breast cancer". Breast Cancer Research and Treatment. 180 (3): 635–646. doi:10.1007/s10549-020-05575-9. PMC   7103015 . PMID   32130619.
  25. Berz, D.; Spira, A.; Gadgeel, S. M.; Anderson, I. C.; Goldman, J. W.; Thompson, J.; Foster, T.; Pritchett, Y. L.; Cisneros, C. G.; Li, C.; Sorrentino, J. A. (1 October 2019). "1537P - Lerociclib (G1T38), an oral CDK4/6 inhibitor, dosed continuously in combination with osimertinib for EGFRmut non-small cell lung cancer: Initial phase Ib results". Annals of Oncology. Abstract Book of the 44th ESMO Congress (ESMO 2019) 27 September – 1 October 2019, Barcelona, Spain. 30: v631. doi: 10.1093/annonc/mdz260.059 . ISSN   0923-7534.
  26. Commissioner, Office of the (12 February 2021). "FDA Approves Drug to Reduce Bone Marrow Suppression Caused by Chemotherapy". FDA. Retrieved 13 February 2021.
  27. Therapeutics, G1 (30 June 2020). "G1 Therapeutics and Boehringer Ingelheim Announce Co-Promotion Agreement for Trilaciclib in Small Cell Lung Cancer in the United States and Puerto Rico". GlobeNewswire News Room. Retrieved 27 December 2020.{{cite web}}: CS1 maint: numeric names: authors list (link)
  28. "Simcere licenses CDK4/6 inhibitor from G1 Therapeutics in $170M deal". www.bioworld.com. Retrieved 5 January 2021.
  29. G1 Therapeutics, Inc. (16 September 2020). "A Phase 1, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Ascending Doses of G1T48 Alone and in Combination With Palbociclib in Women With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer".{{cite journal}}: Cite journal requires |journal= (help)CS1 maint: numeric names: authors list (link)
  30. "G1 Therapeutics nabs $310 million licensing deal for lerociclib". www.thepharmaletter.com. Retrieved 11 December 2020.
  31. "G1 Therapeutics and Genor Biopharma sign agreement for Lerociclib". Express Pharma. 23 June 2020. Retrieved 11 December 2020.
  32. "Latest News & Updates". Arc Therapeutics. Retrieved 10 January 2021.