G1 Therapeutics

G1 Therapeutics

Traded as	Nasdaq: GTHX (2017-24)
Industry	Pharmaceuticals
Founded	2008; 17 years ago (2008)
Founders	Norman Sharpless Kwok-Kin Wong
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
Owner	Pharmacosmos (2024–present)
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]

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]

In September 2024, it was announced that Pharmacosmos had completed its purchase of G1 Therapeutics.[7]

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.[8] The drug's first targeted indication is small cell lung cancer (SCLC).[9] Patients receiving chemotherapy as part of SCLC treatment frequently experience chemotherapy-induced myelosuppression.[10] 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.[11] In June 2020, G1 filed a New Drug Application (NDA) with the Food and Drug Administration (FDA).[12] The application was granted Priority Review with a Prescription Drug User Fee Act (PDUFA) date set for February 15, 2021.[13] In September 2020, G1 launched an expanded access program providing SCLC patients access to trilaciclib while the drug is under FDA review.[14] The FDA approved trilaciclib for use in SCLC on February 12, 2021.[15] 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.[16]

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.[17]

In October 2020, G1 initiated a Phase 3 registrational study (NCT04607668 - PRESERVE 1)[18] evaluating the impact of trilaciclib on myelopreservation and antitumor efficacy in patients receiving chemotherapy for metastatic colorectal cancer.[19] 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.[20] 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.[21] 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.[22]

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.[23][24][25]

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.[26]

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.[27]

Collaborations

• In June 2020, G1 entered into a commercialization agreement with Boehringer Ingelheim to co-promote trilaciclib for SCLC in the United States and Puerto Rico.[28]
• In August 2020, Simcere Pharmaceuticals licensed the development and commercialization rights to trilaciclib for greater China.[29]
• G1 has a non-exclusive clinical supply agreement with Pfizer to provide palbociclib for its rintodestrant/palbociclib breast cancer trial.[30]
• 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).[31]
• In June 2020, G1 licensed the rights to develop lerociclib in the Asia-Pacific region to Genor Biopharma.[32]
• In August 2020, G1 licensed the rights to its preclinical CDK2 inhibitor program to ARC Therapeutics.[33]

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

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. "Pharmacosmos Therapeutics Inc. completed the acquisition of G1 Therapeutics, Inc. from Hercules Capital, Inc. and others". MarketScreener. Retrieved 12 November 2024.
8. "Trilaciclib | intravenous CDK4/6 inhibitor | G1 Therapeutics, Inc". www.g1therapeutics.com. Retrieved 10 January 2021.
9. "FDA Grants Priority Review to Trilaciclib in Small Cell Lung Cancer". Targeted Oncology. Retrieved 5 January 2021.
10. 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.
11. 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.
12. "FDA Grants Trilaciclib Priority Review for Small Cell Lung Cancer". OncLive. Retrieved 11 December 2020.
13. "FDA Grants Priority Review to Trilaciclib to Treat Patients with SCLC". Cancer Network. Retrieved 11 December 2020.
14. "FDA Grants Priority Review to Trilaciclib in Small Cell Lung Cancer". Targeted Oncology. Retrieved 11 December 2020.
15. "FDA Approves Cosela (trilaciclib) to Decrease the Incidence of Chemotherapy-Induced Myelosuppression". Drugs.com. Retrieved 17 February 2021.
16. "NCCN Clinical Practice Guidelines in Oncology". www.nccn.org. Retrieved 25 March 2021.
17. "The I-SPY Trials". www.ispytrials.org. Retrieved 18 February 2021.
18. 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)
19. 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)
20. 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)
21. 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)
22. 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)
23. 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)
24. "Rintodestrant - G1 Therapeutics - AdisInsight". adisinsight.springer.com. Retrieved 11 December 2020.
25. 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.
26. 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.
27. Commissioner, Office of the (12 February 2021). "FDA Approves Drug to Reduce Bone Marrow Suppression Caused by Chemotherapy". FDA. Retrieved 13 February 2021.
28. 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.
29. "Simcere licenses CDK4/6 inhibitor from G1 Therapeutics in $170M deal". www.bioworld.com. Retrieved 5 January 2021.
30. 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)
31. "G1 Therapeutics nabs $310 million licensing deal for lerociclib". www.thepharmaletter.com. Retrieved 11 December 2020.
32. "G1 Therapeutics and Genor Biopharma sign agreement for Lerociclib". Express Pharma. 23 June 2020. Retrieved 11 December 2020.
33. "Latest News & Updates". Arc Therapeutics. Retrieved 10 January 2021.

External Links

• Official website
• G1 Corporate Presentation
• Business data for G1 Therapeutics: Yahoo Finance Nasdaq Reuters SEC filings
• G1 Therapeutics on clinicaltrials.gov
• Cosela