UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): October 1, 2019 (
(Exact name of registrant as specified in its charter)
| |
|
| ||
| (State or other jurisdiction of incorporation) |
(Commission File Number) |
(IRS Employer Identification No.) |
| |
| |||
| (Address of principal executive offices) |
(zip code) |
Registrant’s telephone number, including area code: (
(former address)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| |
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| |
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| |
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| |
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class |
Trading Symbol |
Name of each exchange on which registered | ||
| |
|
|
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (17 CFR §230.405) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR §240.12b-2).
Emerging Growth Company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
| Item 8.01 | Other Events. |
On September 28, 2019, G1 Therapeutics, Inc. (the “Company”) issued a press release announcing updated data at ESMO 2019 from randomized Phase 2 trial of trilaciclib in combination with chemotherapy in metastatic triple-negative breast cancer demonstrating significant improvement in overall survival. These data were presented at the European Society for Medical Oncology (ESMO) 2019 Congress in Barcelona, Spain. A copy of the press release is attached hereto as Exhibit 99.1.
On September 29, 2019, the Company issued a press release announcing preliminary results from a Phase 1/2a dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in patients with estrogen receptor-positive, HER2-negative (ER+, HER2-) breast cancer. These data were presented at ESMO in Barcelona, Spain. A copy of the press release is attached hereto as Exhibit 99.2.
The Company held an Investor & Analyst Event on September 29, 2019 in Barcelona, Spain. A copy of the event materials is attached hereto as Exhibit 99.3.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits
| Exhibit |
Description | |||
| 99.1 |
||||
| 99.2 |
||||
| 99.3 |
||||
| 104 |
Cover Page Interactive Data File (embedded within the Inline XBRL document). | |||
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
| G1 THERAPEUTICS, INC. | ||
| By: |
/s/ James Stillman Hanson | |
| James Stillman Hanson | ||
| General Counsel | ||
Date: October 1, 2019
EXHIBIT 99.1
G1 Therapeutics Presents Updated Data at ESMO 2019 from Randomized Phase 2 Trial of Trilaciclib in Combination with Chemotherapy in Metastatic Triple-Negative Breast Cancer Demonstrating Significant Improvement in Overall Survival
— Trial results published simultaneously in The Lancet Oncology —
— Company also to present updated Phase 2 results demonstrating myelopreservation benefits in small cell lung cancer (SCLC) patients receiving trilaciclib and chemotherapy in combination with Tecentriq® —
— Company to begin rolling New Drug Application (NDA) submission for SCLC in 4Q19 —
— Company to host investor and analyst event, webcast and conference call at 12:45 p.m. ET on September 29, 2019 —
RESEARCH TRIANGLE PARK, N.C. and BARCELONA, SPAIN, Sept. 28, 2019 (GLOBE NEWSWIRE) — G1 Therapeutics, Inc. (Nasdaq: GTHX), a clinical-stage oncology company, today reported preliminary overall survival (OS) data from the company’s randomized Phase 2 trial of trilaciclib in combination with chemotherapy for the treatment of metastatic triple-negative breast cancer (mTNBC). In the trial, median overall survival for patients treated with trilaciclib in combination with a chemotherapy regimen of gemcitabine/carboplatin (GC) was 20.1 months, compared with 12.6 months for patients receiving chemotherapy alone. These data were reported as part of a late-breaking oral presentation (LBA22) at the European Society for Medical Oncology (ESMO) 2019 Congress and featured in a concurrent publication in The Lancet Oncology.
Updated data from a separate randomized Phase 2 trial of trilaciclib in small cell lung cancer (SCLC) will be presented during a poster session (1742PD) on Sunday, September 29 at ESMO 2019 in Barcelona, Spain.
“Triple-negative breast cancer is the most aggressive form of breast cancer and tends to have a poorer prognosis than other breast cancers. We need new therapeutic approaches that improve outcomes for women diagnosed with triple-negative breast cancer,” said Joyce A. O’Shaughnessy, M.D., Baylor University Medical Center, Texas Oncology, U.S. Oncology, and lead investigator for the trial. “As an oncologist specializing in triple-negative breast cancer, I am encouraged that trilaciclib has the potential to improve the survival of patients diagnosed with this disease.”
“Trilaciclib is a first-in-class therapy that has improved outcomes for people with cancer being treated with chemotherapy in four randomized Phase 2 trials. The findings from these trials in small cell lung cancer and triple-negative breast cancer indicate that the clinical benefits of trilaciclib are meaningful and context-dependent,” said Raj Malik, M.D., Chief Medical Officer and Senior Vice President, R&D. “In metastatic triple-negative breast cancer, the benefit manifests as improved overall survival. In small cell lung cancer, patients experience myelopreservation benefits, including reduced rates of neutropenia, anemia and other chemotherapy-related side effects, and a corresponding decrease in the use of rescue therapies required to address those toxicities. Importantly, patient-reported outcome measures across all of our trials showed that trilaciclib improved the patient experience on chemotherapy.”
Mark Velleca, M.D., Ph.D., Chief Executive Officer, added: “Based on feedback from our pre-NDA meeting with the FDA, we will begin a rolling NDA submission for small cell lung cancer in the fourth quarter of this year, which we expect to complete in the second quarter of 2020. We have also had initial discussions with the FDA regarding development of trilaciclib in triple-negative breast cancer, including the preliminary design of a Phase 3 trial. In 2020, we plan to initiate a Phase 3 trial in triple-negative breast cancer and a Phase 3 trial in colorectal cancer, with the goal of demonstrating the benefits of trilaciclib to patients receiving chemotherapy for multiple tumor types.”
Overall survival benefit in mTNBC
The randomized, open-label Phase 2 study (NCT02978716) of trilaciclib in combination with GC, a current standard of care for TNBC, enrolled 102 patients who had received up to two prior chemotherapy regimens for locally recurrent or metastatic TNBC. In this three-arm trial, all three groups received a chemotherapy regimen of GC. Patients were randomized to receive GC only (Group 1) or GC plus one of two dosing schedules of trilaciclib: trilaciclib administered on the day of chemotherapy (Group 2) or trilaciclib administered the day prior to and the day of chemotherapy (Group 3). Primary endpoints for the trial included myelopreservation measures; secondary endpoints included additional myelopreservation measures and anti-tumor efficacy measures of overall response rate (ORR), progression-free survival (PFS) and OS. Myelopreservation and preliminary anti-tumor efficacy results from the trial were reported at the 2018 San Antonio Breast Cancer Symposium (press release here). Topline OS findings were announced in June 2019 (press release here); detailed OS results were reported for the first time at ESMO 2019.
Updated results from the trial showed:
| • | The addition of trilaciclib to chemotherapy resulted in a significant increase in OS in both treatment groups compared to chemotherapy alone. |
| • | Compared to GC alone (Group 1), OS was improved for both trilaciclib arms (Groups 2 and 3) with median OS of 12.6 months, 20.1 months and 17.8 months, respectively (Group 2: HR=0.33, p=0.0283; Group 3: HR=0.34, p=0.0023). The median OS for Groups 2 and 3 combined was 20.1 months (HR=0.36, p=0.0015). The median OS for GC alone (Group 1, 12.6 months) was consistent with historical data. |
| • | PFS and ORR were consistent with previously reported data. |
| • | The safety and tolerability of trilaciclib were consistent with previously reported data. |
| • | There have been no serious adverse events attributed to treatment with trilaciclib in this trial. |
| • | Patient-reported outcome (PRO) measures related to anemia were improved in patients receiving trilaciclib versus patients receiving chemotherapy alone. |
| • | As previously reported, primary endpoints (myelopreservation measures) were not met. |
Trilaciclib in SCLC
On Sunday, September 29, G1 Therapeutics will present updated results from its randomized, double-blind, placebo-controlled Phase 2 trial (NCT03041311) evaluating trilaciclib in extensive-stage SCLC patients receiving first-line chemotherapy and the checkpoint inhibitor Tecentriq® (atezolizumab). The findings were consistent with previously reported data (press release here):
| • | Trilaciclib demonstrated myelopreservation benefits, as shown by statistically significant and clinically meaningful improvement in reduction of myelosuppression endpoints, reduction of chemotherapy side effects and reduction of rescue interventions. |
| • | Trilaciclib was well tolerated, with fewer ³ Grade 3 adverse events (AEs) compared to placebo. |
| • | PRO measures related to anemia were improved in patients receiving trilaciclib versus patients receiving placebo. |
| • | Trilaciclib did not adversely impact chemotherapy anti-tumor efficacy as measured by ORR, PFS and OS. |
Additionally, data from another randomized Phase 1b/2 trial of trilaciclib in patients with SCLC receiving first-line chemotherapy were recently published in Annals of Oncology, the official journal of ESMO. Data in this trial demonstrated the myelopreservation benefits of trilaciclib as indicated by statistically significant reduction in clinically relevant consequences of myelosuppression compared to placebo, resulting in fewer supportive care interventions and dose reductions. Trilaciclib did not adversely impact the anti-tumor efficacy of chemotherapy.
Webcast and Conference Call Details
G1 Therapeutics will host a webcast and conference call of its investor and analyst event on Sunday, September 29, 2019, at 6:45 p.m. CEST (12:45 p.m. ET) to review the data being presented at ESMO 2019, as well as long-range development plans for all three of its clinical-stage therapies and commercial plans for trilaciclib. The live call may be accessed by dialing 866-763-6020 (domestic) or 210-874-7713 (international) and entering the conference code: 5878315. A live and archived webcast will be available on the Events & Presentations page of the company’s website at www.g1therapeutics.com. The webcast will be archived on the same page for 90 days following the event.
About Trilaciclib
Trilaciclib is a first-in-class investigational therapy designed to improve outcomes for people with cancer treated with chemotherapy. Based on results from three randomized trials in patients with small cell lung cancer, trilaciclib has received Breakthrough Therapy Designation, and G1 Therapeutics expects to submit marketing applications in the U.S. and Europe for myelopreservation in small cell lung cancer in 2020. In a randomized trial of women with metastatic triple-negative breast cancer, trilaciclib improved overall survival when administered in combination with chemotherapy compared with chemotherapy alone. The company plans to initiate a Phase 3 clinical trial in triple-negative breast cancer and a Phase 3 clinical trial in colorectal cancer in 2020.
About G1 Therapeutics
G1 Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on the discovery, development and delivery of innovative therapies that improve the lives of those affected by cancer. The company is advancing three clinical-stage programs. Trilaciclib is a first-in-class therapy designed to improve outcomes for patients being treated with chemotherapy. Trilaciclib has received Breakthrough Therapy Designation from the FDA; a rolling NDA submission for small cell lung cancer will begin in 4Q19 and is expected to be completed in the second quarter of 2020. Lerociclib is a differentiated oral CDK4/6 inhibitor designed to enable more effective combination treatment strategies. G1T48 is a potential best-in-class oral selective estrogen receptor degrader (SERD) for the treatment of ER+ breast cancer. G1 Therapeutics also has an active discovery program focused on cyclin-dependent kinase targets.
G1 Therapeutics is based in Research Triangle Park, N.C. For additional information, please visit www.g1therapeutics.com and follow us on Twitter @G1Therapeutics.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “expect,” “plan,” “anticipate,” “estimate,” “intend” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements in this news release include, but are not limited to, the therapeutic potential of trilaciclib, the timing for the commencement and completion of marketing applications in the U.S. and Europe for trilaciclib in SCLC, and plans to initiate additional trials in colorectal cancer and TNBC, and are based on the company’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Factors that may cause the company’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in the company’s filings with the U.S. Securities and Exchange Commission, including the “Risk Factors” sections contained therein and include, but are not limited to, the company’s ability to complete clinical trials for, obtain approvals for and commercialize any of its product candidates; the company’s initial success in ongoing clinical trials may not be indicative of results obtained when these trials are completed or in later stage
trials; the inherent uncertainties associated with developing new products or technologies and operating as a development-stage company; and market conditions. Except as required by law, the company assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.
Contact:
Jeff Macdonald
Senior Director, Investor Relations & Corporate Communications
919-907-1944
jmacdonald@g1therapeutics.com
Exhibit 99.2
G1 Therapeutics Presents First Clinical Data on Oral SERD G1T48 Demonstrating Safety and Tolerability in Patients with Advanced Breast Cancer at ESMO 2019
— Company to host investor and analyst event, webcast and conference call
today at 12:45 p.m. ET —
RESEARCH TRIANGLE PARK, N.C. and BARCELONA, SPAIN, Sept. 29, 2019 (GLOBE NEWSWIRE) – G1 Therapeutics, Inc. (Nasdaq: GTHX), a clinical-stage oncology company, today announced preliminary results from a Phase 1/2a dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in patients with estrogen receptor-positive, HER2-negative (ER+, HER2-) breast cancer. In the trial, G1T48 was well tolerated and demonstrated evidence of anti-tumor activity in heavily pre-treated patients. These data were presented as part of a poster session (340P) at the European Society for Medical Oncology (ESMO) 2019 Congress in Barcelona, Spain.
“Based on the promising safety and tolerability of G1T48 shown in this trial and the established efficacy of the SERD class, we believe that G1T48 has the potential to offer women with ER+, HER2- breast cancer an important new treatment option,” said Mark Velleca, M.D., Ph.D., Chief Executive Officer. “The findings in this trial support further development of G1T48, including in first-line and adjuvant settings, and we expect to initiate a first-line Phase 3 pivotal trial in 2020.”
Raj Malik, M.D., Chief Medical Officer and Senior Vice President, R&D added: “The FDA-approved SERD fulvestrant has been shown to be superior to aromatase inhibitors, the current standard of care in adjuvant ER+, HER2- breast cancer. However, the intramuscular route of administration for fulvestrant can be painful for patients and has precluded its use in the adjuvant setting. Our goal in developing G1T48 is to give patients an opportunity to benefit from the efficacy of a SERD at the earliest stages of their disease.”
Results of Phase 1 dose-escalation trial of G1T48 in ER+, HER2- breast cancer
Safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of G1T48 were evaluated in an open-label, dose-escalation Phase 1 trial. The data reported are from 26 post-menopausal women with ER+, HER2- breast cancer who were eligible to receive up to three lines of prior chemotherapy in the metastatic setting and up to three endocrine therapies, including fulvestrant, aromatase inhibitors and tamoxifen, in the metastatic setting. This was a difficult to treat, heavily pre-treated population: 65% of patients had received ³ 3 lines of therapy, 85% of patients had prior treatment with fulvestrant and most had received one or more targeted therapies (e.g., CDK4/6 inhibitor).
Preliminary findings showed:
| • | G1T48 was well tolerated with no dose-limiting toxicities (DLTs) reported at any of the five dose levels (200 mg, 400 mg, 600 mg, 800 mg and 1,000 mg) studied; maximum tolerated dose (MTD) was not reached. |
| • | No patient experienced a serious adverse event (SAE) related to G1T48. |
| • | Treatment emergent adverse events (TEAEs) were mostly Grade 1 and included fatigue, hot flush, diarrhea, headache, nausea and muscle spasms. |
| • | Seven patients remain on treatment. |
| • | There was a dose-dependent increase in drug exposure; dosing with food reduced variability and increased exposure. |
| • | Significant decreases (70-92%) in 18F-FES PET uptake during G1T48 treatment indicated target engagement for all doses tested. |
| • | Of 19 patients with RECIST measurable tumors: |
| • | The clinical benefit rate (complete response + partial response + stable disease for at least 24 weeks) across all doses was 15.8% (three out of 19 patients). |
| • | Seven patients (36.8%) experienced stable disease across all doses. |
| • | One patient (5.3%) experienced a confirmed partial response (600 mg). |
Based on safety and tolerability findings in the Phase 1b portion of this trial, the company selected the 600 mg and 1,000 mg doses of G1T48 for evaluation in the ongoing Phase 2a portion and will use these data to select the dose for pivotal trials. The company plans to initiate a first-line Phase 3 trial of G1T48 in combination with an oral CDK4/6 inhibitor for the treatment of ER+, HER2- breast cancer in 2020.
Webcast and Conference Call Details
G1 Therapeutics will host a webcast and conference call of its investor and analyst event on Sunday, September 29, 2019, at 6:45 p.m. CEST (12:45 p.m. ET) to review the data being presented at ESMO 2019, as well as long-range development plans for all three of its clinical-stage therapies and commercial plans for trilaciclib. The live call may be accessed by dialing 866-763-6020 (domestic) or 210-874-7713 (international) and entering the conference code: 5878315. A live and archived webcast will be available on the Events & Presentations page of the company’s website at www.g1therapeutics.com. The webcast will be archived on the same page for 90 days following the event.
About G1T48
G1T48 is a potential best-in-class oral selective estrogen receptor degrader (SERD) in development for the treatment of estrogen receptor-positive (ER+) breast cancer. Preclinical data have shown that G1T48 is more potent than Faslodex® (fulvestrant), currently the only FDA-approved SERD treatment. Unlike Faslodex®, which is administered as an intramuscular injection, G1T48 has the potential to significantly improve the patient experience with once-daily oral dosing. The Phase 1/2a trial of G1T48 in estrogen receptor-positive, HER2-negative (ER+, HER2-) breast cancer (NCT03455270) is ongoing.
About G1 Therapeutics
G1 Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on the discovery, development and delivery of innovative therapies that improve the lives of those affected by cancer. The company is advancing three clinical-stage programs. Trilaciclib is a first-in-class therapy designed to improve outcomes for patients being treated with chemotherapy. Trilaciclib has received Breakthrough Therapy Designation from the FDA; a rolling NDA submission for small cell lung cancer will begin in 4Q19 and is expected to be completed in the second quarter of 2020. Lerociclib is a differentiated oral CDK4/6 inhibitor designed to enable more effective combination treatment strategies. G1T48 is a potential best-in-class oral selective estrogen receptor degrader (SERD) for the treatment of ER+ breast cancer. G1 Therapeutics also has an active discovery program focused on cyclin-dependent kinase targets.
G1 Therapeutics is based in Research Triangle Park, N.C. For additional information, please visit www.g1therapeutics.com and follow us on Twitter @G1Therapeutics.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “expect,” “plan,” “anticipate,” “estimate,” “intend” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements in this news release include, but are not limited to, the therapeutic potential of G1T48, the timing for next steps with regard to the initiation of a Phase 3 trial of G1T48 in combination with an oral CDK4/6 inhibitor for the treatment of ER+, HER2- breast cancer, the timing of the commencement and completion of marketing applications in the U.S. and Europe for trilaciclib in SCLC, and are based on the company’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Factors that may cause the company’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in the company’s filings with the U.S. Securities and Exchange Commission, including the “Risk Factors” sections contained therein and include, but are not limited to, the company’s ability to complete clinical trials for, obtain approvals for and commercialize any of its product candidates; the company’s initial success in ongoing clinical trials may not be indicative of results obtained when these trials are completed or in later stage trials; the inherent uncertainties associated with developing new products or technologies and operating as a development-stage company; and market conditions. Except as required by law, the company assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.
+++
Contact:
Jeff Macdonald
Senior Director, Investor Relations & Corporate Communications
919-907-1944
jmacdonald@g1therapeutics.com
ESMO 2019 Update 29 September 2019 Exhibit 99.3
Agenda 6:45 – 6:50 p.m. Welcome & G1 Overview Mark Velleca, M.D., Ph.D., Chief Executive Officer 6:50 – 7:05 p.m. Breast Cancer State of the State c. 2019 Lisa Carey, M.D., FASCO, Chief of Hematology/Oncology and Physician-in-Chief, N.C. Cancer Hospital Associate Director of Clinical Sciences, Lineberger Comprehensive Cancer Center 7:05 – 7:15 p.m. ESMO Data Review: Trilaciclib and G1T48 Raj Malik, M.D., Chief Medical Officer and Senior Vice President, R&D 7:15 – 7:30 p.m. Q&A with Dr. Carey, Dr. Malik and Dr. Velleca 7:30 – 7:40 p.m. Pipeline Development Strategy and Regulatory Milestones Raj Malik, M.D., Chief Medical Officer and Senior Vice President, R&D 7:40 – 7:50 p.m. Commercial Opportunity and Strategy John Demaree, Chief Commercial Officer 7:50 – 8:05 p.m. Q&A with Dr. Malik, Mr. Demaree and Dr. Velleca 8:05 – 8:10 p.m. Upcoming Catalysts and Closing Remarks Mark Velleca, M.D., Ph.D., Chief Executive Officer
Forward-looking statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "plan," "anticipate," "estimate," "intend" and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements in this presentation include, but are not limited to, the therapeutic potential of trilaciclib, lerociclib and G1T48, the expected timing of data availability from ongoing clinical trials, the expected timing of initiation of future clinical trials, and the timing for the commencement and completion of marketing applications in the U.S. and Europe for trilaciclib in SCLC, and are based on the Company’s expectations and assumptions as of the date of this presentation. Each of these forward-looking statements involves risks and uncertainties. Factors that may cause the Company’s actual results to differ from those expressed or implied in the forward-looking statements in this presentation are discussed in the Company’s filings with the U.S. Securities and Exchange Commission, including the "Risk Factors" sections contained therein and include, but are not limited to, the Company’s ability to complete clinical trials for, obtain approvals for and commercialize any of its product candidates; the Company’s initial success in ongoing clinical trials may not be indicative of results obtained when these trials are completed or in later stage trials; the inherent uncertainties associated with developing new products or technologies and operating as a development-stage company; the Company’s development of a CDK4/6 inhibitor to reduce chemotherapy-induced myelosuppression is novel, unproven and rapidly evolving and may never lead to a marketable product; and market conditions. Except as required by law, the Company assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.
Welcome & G1 Overview Mark Velleca, M.D., Ph.D. Chief Executive Officer
Small molecule therapeutics for big oncology indications Breakthrough Therapy Designation; begin rolling NDA submission for SCLC in 4Q19, expect to complete in 2Q20 Preliminary OS benefit in mTNBC; initiating Phase 3 trial in 2H20 Initiating Phase 3 mCRC trial in 2H20 G1T48 Lerociclib Less neutropenia and favorable tolerability – advantages in breast cancer (BC) adjuvant setting Data + dose identification in 4Q19 to support pivotal trials Initiating Phase 3 1L BC trial in 2H20 Committed to improving the lives, treatment options and outcomes of people living with cancer Trilaciclib All three therapies have potential to improve outcomes for women with breast cancer in advanced/ metastatic and adjuvant settings Best-in-class potential Differentiated chemistry, favorable tolerability Initiating Phase 3 1L combo trial with CDK4/6i in 2H20
Small cell lung cancer Triple-negative breast cancer Trilaciclib regulatory update Breakthrough Therapy Designation (BTD) Pre-NDA meeting with Hematology Division completed Will begin rolling NDA submission in 4Q19; expect to complete submission in 2Q20 Anticipate MAA submission in 2H20 Productive interactions with Oncology Division Received feedback on Phase 2 data and comments on preliminary Phase 3 trial design Expect to initiate Phase 3 trial in 2H20
Catalysts across all programs in 2019/2020 INDICATION/COMBO 4Q19 1H20 2H20 trilaciclib IV - CDK4/6i 1st-line SCLC (+ etop/carbo) Begin rolling NDA submission for SCLC Complete NDA submission for SCLC MAA filing for SCLC 1st-line SCLC (+ etop/carbo/Tecentriq) 2nd/3rd-line SCLC (+ topotecan) Initiate Phase 3 TNBC trial Metastatic TNBC (+ gem/carbo) Initiate Phase 3 TNBC trial Metastatic CRC (5-FU regimens) Initiate Phase 3 mCRC trial lerociclib Oral - CDK4/6i ER+, HER2- BC (+ Faslodex) Present additional Phase 1b/2a data Initiate Phase 3 BC trial EGFRm NSCLC (+ Tagrisso) G1T48 Oral - SERD ER+, HER2- BC Initiate Phase 3 CDK4/6i combination trial + Present additional data Well funded with $325M cash at end of 2Q19; anticipate 2019 YE cash of $260-270M
Breast Cancer State of the State c. 2019 Lisa A. Carey M.D., FASCO University of North Carolina Lineberger Comprehensive Cancer Center
Disclosures Research funding (to my institution): Innocrin, Nanostring, Novartis, Roche, Seattle Genetics Advisory or consultant role (no personal compensation): G1 Therapeutics, Innocrin, Lilly, Novartis, Seattle Genetics
Epidemiology of Breast Cancer ~ 270,000 new cases per year in the U.S. (+2,500 men) in 2018 85% curable 3.5 million breast cancer survivors (currently in treatment and completed treatment) in the U.S.
Clinical Receptor Phenotype All Breast Cancer HR+ HER2+ Triple Neg
Clinical Receptor Phenotype: Systemic Therapy All Breast Cancer HR+ HER2+ Triple Neg Primary Rx: Endocrine-based Anti-HER2-based Chemo-based
Goals of Therapy Stages I-III / Nonmetastatic Cure No long-term toxicity Stage IV / Metastatic Control Tolerability (acute and chronic)
Goals of Therapy Stages I-III / Nonmetastatic Cure No long-term toxicity Metastatic Control Tolerability (acute and chronic) Willing to tolerate more acute toxicity in order to complete Rx Balance toxicity and outcome Goals of therapy markedly differ
Decision-making Regarding Need for Medical Therapy Tumor size and appearance (grade) Local lymph node involvement Targetable receptors (ER, PR, HER2) Patient factors (comorbidities, age, etc.) Genomic assays (in ER+ HER2-) E.g. Oncotype Dx Recurrence Score, Prosigna, Mammaprint Medical therapy given to reduce risk of recurrence in nonmetastatic disease = “neoadjuvant” or “adjuvant” therapy If distant metastases present, mainstay of lifelong therapy is medical. If nonmetastatic, type and aggressiveness of treatment vary by:
Modern (Neo) Adjuvant Therapy Hormone receptor (ER, PR) + (regardless of HER2): Antiestrogen pills (5-10 years) Chemotherapy (several months) if high risk HER2+ (regardless of hormone receptors): Chemotherapy (several months) Anti-HER2 therapy (1-3 drugs for 1-2 years) “Triple negative” (all receptors negative): Chemotherapy for up to 1 year
Modern (Neo) Adjuvant Therapy Hormone receptor (ER, PR) + (regardless of HER2): Antiestrogen pills (5-10 years) Chemotherapy (several months) if high risk HER2+ (regardless of hormone receptors): Chemotherapy (several months) Anti-HER2 therapy (1-3 drugs for 1-2 years) Trastuzumab + pertuzumab + neratinib Trastuzumab emtansine in residual disease after neoadjuvant chemotherapy + trastuzumab “Triple negative” (all receptors negative): Chemotherapy for up to 1 year Capecitabine x 6m in residual disease after neoadjuvant chemotherapy Future directions: CDK4/6 inhibitors (soon!) PI3K / mTOR inhibitors Better endocrine Rx (oral SERDs!) Genomics to determine duration of Rx Better anti-HER2 drugs CDK4/6 inhibitors Immunotherapy Molecular assays to determine Rx Tailoring (less vs more) in all Immunotherapy Optimized management of toxicities
Breast Cancer Outcomes Have Improved Better chemotherapy drugs and approaches Better endocrine therapy Development of anti-HER2 therapy 1986-1992 2004-2008 Cossetti R J et al. JCO 2015
Nonmetastatic Breast Cancer Outcomes Have Improved Better chemotherapy drugs and approaches Better endocrine therapy Development of anti-HER2 therapy 1986-1992 2004-2008 Cossetti R J et al. JCO 2015 Cost has also increased! Reason for focus on rational Rx
Epidemiology of Metastatic Breast Cancer Approximately 40,000 deaths per year in the U.S., but declining because of advances in therapy, especially in HER2+ disease Median survival ~3 years, but highly variable Prevalent population in U.S. ≈200,000 women
Treatment Based on Tumor Phenotype Advanced Breast Cancer Requiring Therapy ER and/or PR Positive Endocrine therapy +/- additional Rx Refractory to Endocrine therapy ER and/or PR Negative Chemotherapy HER2 Positive Chemotherapy or ET + HER2 targeting HER2 Negative Chemotherapy Additional HER2-targeted drugs
ASCO Guidelines: General Principles ER+ HER2- Endocrine (usually) preferable to chemotherapy in 1st line Targeted agents added to ET (CDK4/6, mTOR, PI3K inhibitors) Any HER2- receiving chemotherapy Single agent chemotherapy preferable to combination Exception: symptomatic, immediately life-threatening Longer duration ↑ outcome but must be balanced against ↑ toxicity No single optimal 1st or later chemotherapy Factors: prior Rx, toxicity, performance status, comorbidity, patient preference HER2+ HER2-directed Rx is mainstay 1st-line: taxane + trastuzumab + pertuzumab; 2nd-line: T-DM1 HR+ HER2+ may consider ET + HER2-Rx or ET alone in selected cases
Endocrine Rx Algorithm in ER+/HER2- (If premenopausal - OA/OS) PRIOR TREATMENT WITH TAMOXIFEN Early relapse Late relapse Aromatase inhibitor (AI) Fulvestrant (SERD) AI + CDK4/6i AI AI + fulvestrant AI + CDK4/6i Tamoxifen Fulvestrant ± palbociclib AI + everolimus AI Tamoxifen (late relapse) PRIOR TREATMENT WITH AI Early relapse Late relapse Fulvestrant ± CDK4/6i AI + everolimus AI Tamoxifen AI Fulvestrant AI + CD4/6i Tamoxifen Depending on prior Rx: Fulvestrant ± CDK4/6i AI + everolimus AI Tamoxifen
CDK4/6 Inhibitor Effect in HR+ HER2- PALOMA2: Ph 3 letrozole + palbo 1stL PFS: 25m vs 14m OS immature MONALEESA7: Ph 3 ET + ribo 1stL pre/perimen Similar PFS impact CDK 4/6i across lines of Rx (~ HR 0.50) OS ↑ in pretreated pts with abemaciclib, ribociclib, (palbo trial immature). HR ~ 0.70-75. No apparent interaction with PIK3CAmt, ESR1mt etc. Abemaciclib single agent activity, different toxicity profile Widely used. More toxic than ET alone. Being studied in (neo)adjuvant, HER2+ MONARCH1: Abema single agent
Alpelisib Added to Fulvestrant in PreRx PIKC3CA mt HR+ HER2- Andre F, NEJM 2019 PIK3CAmt PIK3CAwt SOLAR1 PFS HR 0.65 in mutant group. No OS yet. Toxicity – hyperglycemia (40%), rash (10%)
Fulvestrant Anastrozole P-value CR+ PR 46% 45% NS CBR 78% 74% NS PFS* 17m 14m 0.049 Robertson JFR et al, Lancet 2016 FALCON study: Phase III trial Fulvestrant as single agent =/> AI in 1st line endocrine Rx ET-naïve! OS 5.5m improvement in Phase II FIRST trial Considerations: Prior adjuvant AI (if anything) should augment difference CDK 4/6i trials usually AI 1st-line, fulvestrant later IM administration is an obstacle – little enthusiasm for adjuvant setting Fulvestrant vs AI: 1st-Line
Chemotherapy in HER2-Negative Breast Cancer HR+ Disease Endocrine Rx Endocrine Refractory Disease CHEMOTHERAPY (Chemotherapy for ER+ and TN disease same. However + immunoRx only in TNBC) Triple Negative Disease
Chemotherapy Options Anthracyclines Doxorubicin Epirubicin Liposomal doxorubicin Taxanes Paclitaxel Docetaxel Nab-paclitaxel Vinca alkaloids Vinorelbine Other anti-tubule Eribulin Antimetabolites Methotrexate 5-FU Capecitabine Gemcitabine Alkylating agents Cyclophosphamide Platinum agents Epothilones Ixabepilone General principles TNBC: Taxanes = platinums 1st-line If PDL1+, use nab paclitaxel + atezolizumab immunoRx Combination chemo more toxic but higher response General principles ET-refractory: Same + oral agent (cape) good transition drug Alone or in combinations
Overall Survival in PD-L1+ Tumors with ImmunoRx added to Chemo 25.0 mo (22.6, NE) 15.5 mo (13.1, 19.4) 100 80 60 40 20 0 Overall survival 0 3 6 9 12 15 18 21 24 27 30 33 36 Months Stratified HR = 0.62 (95% CI: 0.45, 0.86) Atezo + nab-P (n = 185) Plac + nab-P (n = 184) OS events, n 64 88 2-year OS (95% CI), % 54% (42, 65) 37% (26, 47) Schmid et al, NEJM 2019 1st line setting – first immunotherapy approval in breast cancer Many many trials pending Less tractable than melanoma, NSCLC, etc. Effect markedly lower in pretreated patients Impassion 130 1st-line TNBC
Summary Nonmetastatic breast cancer is common and curable. Mainstays of therapy = chemotherapy, endocrine therapy, anti-HER2 depending on risk and type of cancer. Challenges – tailoring therapy, identifying if agents active in metastatic disease help reduce risk of recurrence if used (neo)adjuvantly. Metastatic breast cancer is 40,000 women per year in U.S. Longevity after diagnosis increasing, now ~ 3y overall, but not curable. Challenges – reducing toxicity, improving targeted therapies, role of immunotherapy Thank you!
ESMO Data Review: Trilaciclib and G1T48 Raj Malik, M.D. Chief Medical Officer and Senior Vice President, R&D
Trilaciclib mTNBC randomized Phase 2 trial: key findings 102-patient three-arm trial; all groups received gemcitabine/carboplatin (GC), a single-day regimen Group 1 – GC only Group 2 – GC + trilaciclib on day of GC Group 3 – GC + trilaciclib on day prior to and day of GC Both trilaciclib arms showed significant OS improvement compared to control Endpoints for myelopreservation were not achieved in this trial Trilaciclib was well tolerated with improvement in anemia-related PRO measures ESMO 2019: Trilaciclib improves overall survival when given with gemcitabine/carboplatin (GC) in patients with metastatic triple negative breast cancer (mTNBC) in a randomized Phase 2 trial; Abstract #6255 Lancet Oncol 2019; September 28, 2019 http://dx.doi.org/10.1016/S1470-2045(19)30616-3 Now Online First at TheLancet.com: 10.15 CEST, September 28, 2019
ITT population Control (GC only) (Group 1) Trilaciclib + GC (Group 2) Trilaciclib + GC (Group 3) Trilaciclib + GC (Group 2+3) N = 34 N = 33 N = 35 N = 68 Median OS (months) 12.6 20.1 17.8 20.1 HR 0.33 0.34 0.36 p-value 0.028 0.0023 0.0015 Median PFS (months) 5.7 9.4 7.3 8.8 HR 0.60 0.59 0.59 p-value 0.13 0.12 0.063 Significant overall survival benefit with trilaciclib Patients with death - Group 1: 20/34 (58.8%); Group 2: 11/33 (33.3%); Group 3: 14/35 (40.0%) Overall Response Rate (ORR): 33% (Group 1), 50% (Group 2), 37% (Group 3) Group 1: GC only (Day 1/8) (n=34); Group 2: trilaciclib + GC (Day 1/8) (n=33); Group 3: trilaciclib + GC (Day 1/2/8/9) (n=35) ESMO 2019: Trilaciclib improves overall survival when given with gemcitabine/carboplatin (GC) in patients with metastatic triple negative breast cancer (mTNBC) in a randomized Phase 2 trial; Abstract #6255 Results published concurrently in The Lancet Oncology
Significant overall survival benefit with trilaciclib OS benefit greater than PFS suggests immune-mediated effect Based on data as of 17 May 2019 Group 1: GC only (Day 1/8) (n=34); Group 2: trilaciclib + GC (Day 1/8) (n=33); Group 3: trilaciclib + GC (Day 1/2/8/9) (n=35) ESMO 2019: Trilaciclib improves overall survival when given with gemcitabine/carboplatin (GC) in patients with metastatic triple negative breast cancer (mTNBC) in a randomized Phase 2 trial; Abstract #6255 Results published concurrently in The Lancet Oncology 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 1.0 0.9 0.8 0.7 0.6 0.5 0.3 0.2 0.1 0 Months from randomization 34 27 27 26 25 23 21 19 18 16 14 13 13 9 6 6 3 2 1 0 0 0 0 0 0 0 0 Group 1 Patients at risk, n 33 33 32 31 28 26 24 22 20 20 19 17 17 15 13 13 12 10 8 5 3 2 1 1 0 0 0 Group 2 35 35 35 35 32 31 30 26 23 21 21 20 19 17 13 13 9 8 5 3 3 1 1 1 1 1 0 Group 3 Probability of being alive Group 1 Group 2 Group 3 Group 1 Group 2 Group 3 Median OS, months 12.6 20.1 17.8 HR p-value 0.33 0.028 0.34 0.0023
Subgroup No. of patients No. of events HR 95% CI Overall (ITT) 102 (100) 45 0.36 (0·19–0·67) Age <65 years 76 (74·5) 36 0.45 (0·23–0.91) ≥65 years 26 (25·5) 9 0.13 (0·03–0·63) Race White 78 (76·5) 33 0.26 (0·12–0·54) Non-white 24 (23·5) 12 0.92 (0·22–3·84) Liver involvement Yes 26 (25·5) 17 0.33 (0·11–1·01) No 76 (74·5) 28 0.38 (0·18–0·81) Region USA 83 (81·4) 37 0.32 (0·16–0·65) Ex-USA 19 (18·6) 8 0.42 (0·09–2·02) ECOG PS 0 53 (52) 18 0.15 (0·05–0·44) 1 49 (48) 27 0.72 (0·33–1·61) Number of prior lines therapy 0 64 (62·7) 28 0.46 (0·21–0.99) 1 or 2 38 (37·3) 17 0.22 (0·07–0·67) BRCA classification Unknown 66 (64·7) 28 0.42 (0·19–0.92) Positive 8 (7·8) 3 NE (NE–NE) Histological TNBC classification Always 71 (69·6) 31 0.35 (0·17–0·74) Acquired 25 (24·5) 12 0.25 (0·06–1·02) Based on data as of 17 May 2019 • Group 1: GC (Day 1/8) (n=34); Group 2: GC + trilaciclib (Day 1/8) (n=33); Group 3: GC + trilaciclib (Day 1/2/8/9) (n=35) CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; ITT, intention-to-treat; NE, not estimable ESMO 2019: Trilaciclib improves overall survival when given with gemcitabine/carboplatin (GC) in patients with metastatic triple negative breast cancer (mTNBC) in a randomized Phase 2 trial; Abstract #6255 Results published concurrently in The Lancet Oncology OS benefit across all subgroups Pre-specified subgroup analyses 0.031 0.062 0.125 0.250 0.500 1.00 2.00 4.00 GC-only better (Group 1) Trilaciclib better (Groups 2+3)
G1T48 (Oral SERD) Update
G1T48 Phase 1 trial: key findings Well tolerated; favorable safety profile at all dose levels No dose-limiting toxicities observed; maximum tolerated dose not reached AEs mostly Grade 1 18F-FES PET scans – ER occupancy ≥ 80% in doses ≥ 400 mg Preliminary evidence of anti-tumor activity in heavily pre-treated population Phase 1 completed; 600 mg and 1,000 mg dose expansion cohorts enrolling Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer (ABC); Abstract #3587
Favorable tolerability and safety profile; AEs mostly Grade 1 Data cut: 12 August 2019 Drug-related adverse event Grade 1 Grade 2 Grade 3 Grade 4 Total (N=26) Fatigue 6 (23.1%) 1 (3.8%) 1 (3.8%) 0 8 (30.8%) Hot flush 5 (19.2%) 2 (7.7%) 0 0 7 (26.9%) Diarrhea 6 (23.1%) 1 (3.8%) 0 0 7 (26.9%) Headache 4 (15.4%) 0 0 0 4 (15.4%) Nausea 4 (15.4%) 0 0 0 4 (15.4%) Muscle spasms 2 (7.7%) 1 (3.8%) 0 0 3 (11.5%) Myalgia 3 (11.5%) 0 0 0 3 (11.5%) Abdominal distension 1 (3.8%) 1 (3.8%) 0 0 2 (7.7%) Musculoskeletal stiffness 1 (3.8%) 1 (3.8%) 0 0 2 (7.7%) Cough 0 1 (3.8%) 0 0 1 (3.8%) Hypoglycemia 0 1 (3.8%) 0 0 1 (3.8%) Lymphopenia 0 1 (3.8%) 0 0 1 (3.8%) Pain (musculoskeletal chest) 0 1 (3.8%) 0 0 1 (3.8%) AEs occurring in ≥3 patients or ≥CTCAE Grade 2; All TEAEs; AEs regardless of causality Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer (ABC); Abstract #3587
PK/PD profile: robust target engagement ≥ 80% decrease in uptake at doses ≥ 400 mg Generally dose-dependent increases in exposure Food decreased variability and increases exposure Patients in expansion cohorts being dosed with food PK summary Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer (ABC); Abstract #3587 PD: 18F-FES PET uptake in tumors 0 -20 -40 -60 -80 -100 Change from baseline (%) Individual patients
Heavily pre-treated patient population ~85% of patients had prior fulvestrant therapy ~65% of patients had received at least three lines of therapy N = 26 Patients % Prior fulvestrant 22 84.6% Prior CDK4/6 inhibitor 20 76.9% Prior chemotherapy 13 50.0% Last prior therapy duration ≤ 6mos 11 42.3% ≥ 3 lines of therapy 17 65.4% Visceral disease 16 61.5% Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer (ABC); Abstract #3587
Efficacy demonstrated in heavily pre-treated population ORR=(CR+PR); CBR=(CR+PR+SD≥24 weeks) Response evaluable pts (N=19) ORR 1 (5.3%) CBR 3 (15.8%) Patient characteristics associated with PD by 8 weeks: Visceral disease ≥ 3 lines of prior therapy ≤ 6 months on most recent prior therapy Prior chemotherapy in metastatic setting Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer (ABC); Abstract #3587 Patient Characteristics
ESMO 2019: key findings Trilaciclib improved overall survival when added to GC regimen Well tolerated with improvement in anemia-related PRO measures Phase 3 trial beginning in 2H20 Favorable safety and tolerability profile Evidence of anti-tumor efficacy in heavily pre-treated population Phase 3 trial beginning in 2H20 Trilaciclib: mTNBC G1T48
Q&A Dr. Carey, Dr. Malik & Dr. Velleca
Pipeline Development Strategy and Regulatory Milestones Raj Malik, M.D. Chief Medical Officer and Senior Vice President, R&D
Trilaciclib: context-dependent efficacy Weiss et al, Annals of Oncology 2019 He et al, Science Translational Medicine 2017 Bisi et al, Mol Cancer Ther., 2016 Tan et al, Lancet Oncology 2019 Zhang et al, Nature 2018 Jerby-Arnon et al, Cell 2018 Goel et al, Nature 2017 Deng et al, Cancer Discovery 2017 Alters the proliferation kinetics and composition of intratumor T-cell subsets to favor increased effector function Enhances T-cell activation Increases antigen processing and presentation on tumor cells Reduces immunosuppressive function of regulatory cells Preserves immune cell function and potentially enhances anti-tumor immunity T cell Tumor M G2 G1 S Trilaciclib (CDK4/6 inhibitor) Normal Cell Proactive protection of HSPC prevent chemotherapy-induced myelosuppression HSPC Neutrophil Erythrocyte Platelets T lymphocyte B lymphocyte Reduces occurrence and duration of severe neutropenia Reduces anemia and thrombocytopenia Reduces need for supportive care (growth factors, transfusions, chemotherapy dose reductions) Preserves lymphocytes Transient G1 arrest during chemotherapy SCLC trials: myelopreservation TNBC trial: OS improvement
Trilaciclib benefits linked to setting Primary Benefit: Myelopreservation Primary Benefit: Anti-Tumor Efficacy Chemotherapy schedule Multi-day regimens Single-day regimens Tumor type --- Tumor microenvironments more favorable to immune modulation Settings/indications: SCLC (etoposide + platinum, topotecan) 1L mCRC (5-FU regimens) Neoadjuvant TNBC (doxorubicin + cyclophosphamide + taxane) 1L mTNBC (TBD +/- anti-PD-L1) 1L mBC (taxane) Two-pronged development strategy: myelopreservation and anti-tumor efficacy
Development plan targets broad myelopreservation label and anti-tumor efficacy label for specific tumors DISEASE OF INTEREST CHEMO REGIMENS 2020 2021 2022 2023 2024 2025 Myelopreservation 1L SCLC Etoposide + platinum, topotecan 1L mCRC 5-FU regimens Neoadj TNBC Doxo + cyclo + taxane Anti-tumor efficacy 1L mTNBC TBD +/- anti-PD-L1 1L mBC Taxane Denotes timing for completion of FDA review and potential U.S. approval; RoW is ~2Q later for all indications except SCLC. End of shading highlights data readout; dashed box indicates preparing, filing and regulatory review period. Partnering to enable expansion in other tumor types: e.g. NSCLC
DISEASE OF INTEREST COMBO DRUG 2020 2021 2022 2023 2024 2025 2026 2027 G1T48 1L ER+ mBC CDK4/6i 2L ER+ mBC Everolimus Neoadjuvant BC* N/A Adjuvant ER+ BC NA lerociclib 1L ER+ mBC Fulvestrant Adjuvant ER+ BC Aromatase inhibitor Lerociclib and G1T48: improving patient care in advanced/metastatic and adjuvant settings Denotes timing for completion of FDA review and potential U.S. approval; RoW is ~2Q later for all indications. End of shading highlights data readout; dashed box indicates preparing, filing and regulatory review period. * Neoadjuvant trial enables adjuvant trial G1T48 and lerociclib partnering to enable expansion in other indications
Commercial Opportunity and Strategy John Demaree Chief Commercial Officer
Trilaciclib provides context-dependent efficacy: myelopreservation or improved survival TNBC: OS Improvement SCLC: Myelopreservation PLACEBO + CHEMOTHERAPY TRILACICLIB + CHEMOTHERAPY Patients (intent-to-treat population) 120 125 P-VALUE⁺ Mean duration (in days) of severe neutropenia in cycle 1 (SD) 4 (5.2) 1 (2.3) <0.0001 Occurrence of severe neutropenia 64 (53.3%) 16 (12.8%) <0.0001 Occurrence of RBC transfusions on/after 5 weeks 32 (26.7%) 19 (15.2%) 0.0207 Cumulative incidence RBC transfusions on/after 5 wks: event rate per 100 wks 3.2 1.5 0.0020 Occurrence of Grade 3/4 anemia 39 (32.5%) 26 (20.8%) 0.0188 Occurrence of Grade 3/4 thrombocytopenia 44 (36.7%) 26 (20.8%) 0.0081 Improved patient experience Trilaciclib is a first-in-class investigational therapy designed to improve outcomes for people with cancer treated with chemotherapy G1 market research suggests substantial share uptake in all indicated patients
~1 million chemo-treated patients in planned indications *Source: Secondary epi sources, 2027 estimates **EP refers to any regimen that includes etoposide + platinum; GC refers to gemcitabine/carboplatin; AC refers to any regimen that includes Adriamycin and cyclophosphamide; 5-FU refers to any regimen that includes fluorouracil (e.g., FOLFOX). In addition to CRC, pancreatic cancer, gastroesophageal cancer and squamous cell carcinoma of the head and neck (SCCHN) are also treated with 5-FU regimens (% currently treated with 5-FU regimens varies by tumor type and region) ***Source: SCLC and TNBC: G1 Therapeutics’ completed trials; CRC and Adjuvant BC: number of cycles for eligible chemo regimens from Decision Resources Group Treatment Landscape and Forecast Assumptions 2018 Reports (CRC and BC) Global Chemotherapy Treated Incident Patients (G7)* % currently treated with eligible chemo regimen** ~100% (EP) 50% (topotecan or EP) 55% (GC, taxane or IO + chemo) 80% (5-FU) 70% (5-FU) 50% (5-FU) 65% (AC) 50% (AC) 40% (AC) Estimated mean # of cycles*** 4-6 3-4 7-8 11-23 4-12 12 8 SCLC: 68K TNBC 20K CRC: >500K Adjuvant BC: >350K 8 8 Potential to be used for myelopreservation in the same patient across multiple lines of therapy
Trilaciclib go-to-market strategy Planning Capabilities Comprehensive launch plans across all functions All milestones on schedule Trilaciclib supply will be available at approval Hired experienced key functional talent at G1 Utilizing contractors for initial functional-level buildouts, including sales Maintaining strategic agility to scale as needed for future launches Partner Leverage partner’s capabilities and scale to maximize uptake and expand development G1 partner to commercialize ex-US G1 intends to maintain a significant US role Commercial team: significant oncology launch experience (XTANDI, Tagrisso, Tecentriq, Femara)
G1T48 and lerociclib: >350,000 1L and adjuvant BC patients Duration** 14 months 33 months 60 months 25 months 60 months *Source: Secondary epi sources, 2027 estimates **Duration estimates based on similar trial results in the same or similar patient populations as planned trials G1T48 lerociclib Global HR+/HER2- Breast Cancer Treated Incident Patients (G7)* Adjuvant use: long treatment duration requires well tolerated profile 223,000 223,000
Q&A Dr. Malik, Mr. Demaree & Dr. Velleca
Upcoming Catalysts and Closing Remarks Mark Velleca, M.D., Ph.D. Chief Executive Officer
Catalysts across all programs in 2019/2020 INDICATION/COMBO 4Q19 1H20 2H20 trilaciclib IV - CDK4/6i 1st-line SCLC (+ etop/carbo) Begin rolling NDA submission for SCLC Complete NDA submission for SCLC MAA filing for SCLC 1st-line SCLC (+ etop/carbo/Tecentriq) 2nd/3rd-line SCLC (+ topotecan) Initiate Phase 3 TNBC trial Metastatic TNBC (+ gem/carbo) Initiate Phase 3 TNBC trial Metastatic CRC (5-FU regimens) Initiate Phase 3 mCRC trial lerociclib Oral - CDK4/6i ER+, HER2- BC (+ Faslodex) Present additional Phase 1b/2a data Initiate Phase 3 BC trial EGFRm NSCLC (+ Tagrisso) G1T48 Oral - SERD ER+, HER2- BC Initiate Phase 3 CDK4/6i combination trial + Present additional data Well funded with $325M cash at end of 2Q19; anticipate 2019 YE cash of $260-270M
Lisa A. Carey, M.D., FASCO is the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research in the Department of Medicine at the University of North Carolina (UNC). She graduated from Wellesley College, then received her medical degree from the Johns Hopkins University School of Medicine where she remained for her residency in Internal Medicine followed by a fellowship in Medical Oncology and an advanced degree in Clinical Investigations. Dr. Carey joined the UNC faculty and Lineberger Comprehensive Cancer Center in 1998. Currently she is the Chief of the Division of Hematology and Oncology and Physician-in-Chief of the North Carolina Cancer Hospital. In addition, she has a role at Lineberger Comprehensive Cancer Center as the Associate Director for Clinical Sciences. Dr. Carey has a longstanding research interest in the clinical application of laboratory findings in breast cancer, with a particular interest in the clinical implications of different molecular subtypes of breast cancer. She designs and leads clinical trials of novel drugs and approaches, and is a close collaborator with several laboratory investigators and epidemiologists. Dr. Carey has served in many roles for the American Society of Clinical Oncology (ASCO), the American Association for Cancer Research (AACR) and the NCI. She was awarded the Doris Duke Clinician Scientist Award in 1999, a Career Development Award from the National Cancer Institute (NCI) in 2000, was inducted into the Johns Hopkins Society of Scholars in 2008, was awarded the NCI Director's Service Award in 2011, and was named co-chair of the Alliance National Cooperative Group Breast Committee in 2016. Dr. Carey was honored to become a member of the Komen Scientific Advisory Board as of April 2018 and in June 2019 earned the distinction of Fellow of the American Society of Clinical Oncology (FASCO). Lisa Carey, M.D., FASCO Chief of Hematology/Oncology and Physician-in-Chief, N.C. Cancer Hospital Associate Director of Clinical Sciences, Lineberger Comprehensive Cancer Center
jmacdonald@g1therapeutics.com www.g1therapeutics.com Jeff Macdonald 919.907.1944