Spectrum Pharmaceuticals Provides Poziotinib Update

On December 19, 2018 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), reported that based on a subset of data from MD Anderson’s ongoing Phase 2 study, the U.S. Food and Drug Administration (FDA) did not grant Breakthrough Therapy Designation (BTD) to poziotinib for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 20 mutations (Press release, Spectrum Pharmaceuticals, DEC 19, 2018, View Source;19.htm [SID1234532181]). The company’s overall development plan and timeline for a New Drug Application (NDA) filing based on the first cohort of the ZENITH20 trial remains unchanged.

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Breakthrough Therapy Designation is one of several FDA programs designed to expedite the review of drugs to treat serious or life threatening conditions. Spectrum’s BTD application included data from 30 patients from the MD Anderson Phase 2 study who had failed platinum-based chemotherapy. The data demonstrated a confirmed objective response rate of 40% and median duration of response of 6.6 months. The safety profile in this subset was consistent with historical data published on poziotinib and other tyrosine kinase inhibitors. The historical objective response rates for mutation specific NSCLC patients range between 0% and 8% with tyrosine kinase inhibitors and for non-mutation specific NSCLC patients range between 0.8% and 22.9% with other treatments.

"Our enthusiasm for poziotinib, our commitment to the program, and our overall development plan remain unchanged," said Joe Turgeon, President and Chief Executive Officer of Spectrum Pharmaceuticals. "We will continue to work with the FDA to achieve the fastest route to approval of poziotinib based on our ZENITH20 study."

ZENITH20 is a Spectrum-sponsored, open-label, single-arm, multi-center, global Phase 2 study evaluating more than 300 NSCLC patients with EGFR or HER2 exon 20 insertion mutations. The study consists of four cohorts, each of which is independently powered for a pre-specified statistical hypothesis.

"Poziotinib’s overall development program is robust, and the clinical profile remains very attractive in an area of high unmet need," said Francois Lebel, M.D., F.R.C.P.C, Chief Medical Officer of Spectrum Pharmaceuticals. "Data required for the NDA filing for previously treated NSCLC patients with EGFR exon 20 insertion mutations is expected to come from an 87-patient cohort in our ZENITH20 study. We expect to complete enrollment in this cohort in the first quarter of 2019, and announce topline data in the second half of 2019."

11500 S. Eastern Ave., Ste. 240 • Henderson, Nevada 89052 • Tel: 702-835-6300 • Fax: 702-260-7405 • www.sppirx.com • NASDAQ: SPPI

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Conference Call Details:
Wednesday, December 19, 2018 at 4:30 p.m. Eastern/1:30 p.m. Pacific
Domestic: (877) 837-3910, Conference ID# 1577888
International: (973) 796-5077, Conference ID# 1577888
The conference call will also be webcast live. To access the webcast, please visit the Investor Relations page of the Spectrum Pharmaceuticals website at View Source
For interested individuals unable to join the call, a replay will be available from December 19, 2018 @ 7:30 p.m. ET/4:30 p.m. PT through December 26, 2018, until 7:30 p.m. ET/4:30 p.m. PT.
Domestic Replay Dial-In: (855) 859-2056, Conference ID# 1577888
International Replay Dial-In: (404) 537-3406, Conference ID# 1577888

About Poziotinib
Poziotinib is a novel, oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) that inhibits the tyrosine kinase activity of EGFR as well as HER2 and HER4. Importantly this leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer. Spectrum received exclusive license from Hanmi Pharmaceuticals to develop, manufacture, and commercialize poziotinib worldwide, excluding Korea and China. Poziotinib is currently being investigated by Spectrum and Hanmi in several mid-stage trials in multiple solid tumors.

About ZENITH20

The ZENITH20 study is Spectrum-sponsored, Phase 2, open-label, single-arm, multi-center, global study for patients with EGFR or HER2 exon 20 insertion mutations in NSCLC. It consists of four cohorts, each of which is an independent study with pre-specified statistical hypotheses and statistical power. There are two cohorts in the previously-treated setting and two in the first-line setting. The full poziotinib targeted therapy clinical program is focused on four development areas for EGFR and HER2 mutations, including previously treated NSCLC, first-line NSCLC, treatment of other solid tumors and combination therapy.

Anixa Biosciences Announces Completion of Pre-Sub Meeting with FDA for its Cchek™ Cancer Diagnostic Test

On December 19, 2018 Anixa Biosciences, Inc. (NASDAQ: ANIX), a biotechnology company focused on using the body’s immune system to fight cancer, reported that it completed a Pre-Submission (Pre-Sub) meeting with the US FDA on December 17, 2018 (Press release, Anixa Biosciences, DEC 19, 2018, View Source [SID1234532175]).

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The meeting was focused on discussing Anixa’s Cchek test, an artificial intelligence (AI) based liquid biopsy for the early detection of cancer. Specifically, the discussion focused on using Cchek for prostate cancer testing, as prostate cancer will be the first commercial application.

Dr. Amit Kumar, President and CEO of Anixa Biosciences said, "The meeting was very positive and productive, with discussions that included the intended use of the test, the path for regulatory approval, and the use of AI. We are eager to move Cchek-Prostate towards commercialization." Dr. Kumar continued, "Standard of care for screening for prostate cancer includes a prostate specific antigen (PSA) measurement, followed by a digital rectal exam (DRE). It is well known that these current tests are imperfect, and cause hundreds of thousands of men to undergo painful, expensive and risk-laden biopsies that are negative and may be unnecessary. Our preliminary data, which we presented to the FDA, demonstrates that Cchek-Prostate could potentially eliminate a large number of these unnecessary procedures. The FDA was very supportive and appreciated us initiating the dialogue with them. As we continue through the regulatory process, we anticipate additional productive meetings and submissions with the FDA."

Anixa Biosciences expects the official minutes of the Pre-Sub meeting to be available in January. On January 24, 2019 Anixa plans to hold a conference call where it will discuss the commercialization path and timeline for Cchek-Prostate, as well as an update on its CAR-T therapeutics program. The details of the conference call will be provided at a later date.

GlaxoSmithKline plc and Pfizer Inc to form new world-leading Consumer Healthcare Joint Venture

On December 19, 2018 GlaxoSmithKline plc (LSE/NYSE: GSK) reported that it has reached agreement with Pfizer Inc to combine their consumer health businesses into a new world-leading Joint Venture, with combined sales of approximately £9.8 billion ($12.7 billion)[1] (Press release, GlaxoSmithKline, DEC 19, 2018, View Source [SID1234532172]). GSK will have a majority controlling equity interest of 68% and Pfizer will have an equity interest of 32% in the Joint Venture.

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The proposed all-equity transaction represents a compelling opportunity to build on the recent buyout of Novartis’ stake in GSK Consumer Healthcare, to create a new world-leading consumer healthcare business and to deliver further significant shareholder value. The proposed transaction also supports GSK’s key priority of strengthening its pharmaceuticals business over the next few years by increasing cashflows and providing an effective pathway through the separation of GSK Consumer Healthcare to build further support for investment in its R&D pipeline.

New Consumer Healthcare Joint Venture

The new Joint Venture will be well-positioned to deliver stronger sales, cash flow and earnings growth driven by category leading Power Brands, science-based innovation and substantial cost synergies. The combination will bring together two highly complementary portfolios of trusted consumer health brands, including GSK’s Sensodyne, Voltaren and Panadol and Pfizer’s Advil, Centrum and Caltrate. The Joint Venture will be a category leader in Pain Relief, Respiratory, Vitamin and Mineral Supplements, Digestive Health, Skin Health and Therapeutic Oral Health. The Joint Venture will be the global leader in OTC products with a market share of 7.3% ahead of its nearest competitor at 4.1% and have number 1 or 2 market share positions in all key geographies, including the US and China.

The proposed transaction is expected to realise substantial cost synergies, with the Joint Venture expected to generate total annual cost savings of £0.5 billion by 2022 for expected total cash costs of £0.9 billion and non-cash charges of £0.3 billion. Planned divestments targeting around £1 billion of net proceeds are expected to cover the cash costs of the integration. Up to 25% of the cost savings are intended to be reinvested in the business to support innovation and other growth opportunities. Overall the Joint Venture will target an Adjusted operating margin percentage in the ‘mid-to-high 20’s’ by 2022.

GSK expects the proposed transaction to be accretive to Total earnings in the second full year following closing, reflecting the impact and timing for the costs of integration; and to be accretive to Adjusted earnings and free cashflow in the first full year after closing

Future separation

The proposed transaction is transformational to the scale of GSK’s Consumer Healthcare business. Within 3 years of the closing of the transaction, GSK intends to separate the Joint Venture via a demerger of its equity interest and a listing of GSK Consumer Healthcare on the UK equity market. Over this period, GSK will substantially complete the integration and expects to make continued progress in strengthening its Pharmaceuticals business and R&D pipeline.

The intended separation of the Group will allow the two resulting companies to be established with appropriate capital structures for their future investment needs and capital allocation priorities. The new consumer healthcare company with its more durable cash flows will be able to support higher leverage levels than the GSK Group today, creating the opportunity on separation to reduce the leverage in the new Pharmaceuticals/Vaccines company.

Dividend expectations

GSK remains committed to its current dividend policy and confirms it continues to expect to pay 80 pence per share in dividends for 2018. Recognising the significance of this proposed transaction and the importance of dividends to shareholders, the company is today confirming that it expects to pay dividends of 80 pence per share for 2019.

Going forward, the proposed transaction enhances prospects for the Consumer Healthcare business and supports the development of GSK’s Pharmaceuticals business. With expected improvements in both businesses, GSK expects to be well positioned to deliver returns to shareholders alongside continued investment in its strategic priorities.

Emma Walmsley, Chief Executive Officer, GSK, said:

"Eighteen months ago, I set out clear priorities and a capital allocation framework for GSK to improve our long-term competitive performance and to strengthen our ability to bring new breakthrough medicines and better healthcare products to people around the world. We have improved our operating performance and have set out a new approach to R&D. We have also started to reshape the Group’s portfolio through prioritisation of R&D programmes, acquisitions such as that proposed with the oncology biopharmaceutical company, TESARO, the minority buy-out of the consumer healthcare business and a series of non-core product divestments.

"The transaction we have announced today is a unique opportunity to accelerate this work. Through the combination of GSK and Pfizer’s consumer healthcare businesses we will create substantial further value for shareholders. At the same time, incremental cashflows and visibility of the intended separation will help support GSK’s future capital planning and further investment in our pharmaceuticals pipeline.

"With our future intention to separate, the transaction also presents a clear pathway forward for GSK to create a new global Pharmaceuticals/Vaccines company, with an R&D approach focused on science related to the immune system, use of genetics and advanced technologies, and a new world-leading Consumer Healthcare company.

"Ultimately, our goal is to create two exceptional, UK-based global companies, with appropriate capital structures, that are each well positioned to deliver improving returns to shareholders and significant benefits to patients and consumers."

Approvals and closing

The proposed transaction is subject to approval by GSK shareholders and conditional upon the receipt of certain anti-trust authority approvals. Subject to these approvals, the transaction is expected to close in the second half of 2019. The Board intends to recommend that shareholders vote in favour of the proposed transaction.

Analyst conference call details
09:00 UK Wednesday 19 December

Listen only line: UK: +44 (0) 20 7136 5118 US: +1 857 244 8211 Passcode: 625 844 62
UK toll free: 080 0085 8265 US toll free: +1 877 364 0946 Global access numbers

Line with Q&A: UK: +44 (0) 20 7365 4163 US: +1 857 244 7313 Passcode: 771 241 13
UK toll free: 080 8234 7616 US toll free: +1 877 280 4956 Global access numbers

Slides will be available on the GSK website one hour prior to the call.

Principal terms and conditions of the Transaction

New Joint Venture

GSK and Pfizer have today entered into an agreement under which, upon closing of the proposed transaction, Pfizer will contribute its consumer healthcare business to GSK’s existing consumer healthcare business in return for equity shares in this business. As a result, a new Joint Venture will be created in which GSK will have a controlling 68% equity interest and Pfizer a 32% equity interest.

GSK and Pfizer have provided customary and broadly reciprocal representations, warranties and indemnities to each other in respect of their respective businesses that will be included in the Joint Venture, which are subject to customary limitations of liability.

Combined 2017 global sales for the Joint Venture were approximately £9.8 billion ($12.7 billion)[2]. The Joint Venture will be a category leader in Pain Relief, Respiratory, Vitamin and Mineral Supplements, Digestive Health, OTC Skin Health and Therapeutic Oral Health and will have the largest global market share in OTC at 7.3% ahead of its nearest competitor at 4.1%. The Joint Venture is expected to have number 1 or 2 market share positions in all key geographies, including the US, Western, Central and Eastern Europe, China, India and Australasia.

The Joint Venture will operate under the GSK Consumer Healthcare name in all territories where GSK and Pfizer have a presence, with the exception of GSK’s interest in its listed subsidiary in Nigeria which will be excluded from the Joint Venture. The assets within the scope of, and the proceeds of, GSK’s proposed divestment of Horlicks and other Consumer Healthcare nutrition products to Unilever will not be included in the Joint Venture.

Until separation, the Joint Venture will be consolidated in GSK’s financial statements and is not expected to carry any external debt.

Governance and leadership

The Joint Venture will be subject to a shareholders’ agreement between GSK and Pfizer, under which GSK will have 6 directors and Pfizer 3 directors on the board of the joint venture company. GSK will have control of the joint venture company through the board, while Pfizer will enjoy customary minority shareholder protections.

Emma Walmsley will be Chair of the new Joint Venture until separation. Brian McNamara, currently CEO GSK Consumer Healthcare, will be CEO of the new Joint Venture and Tobias Hestler, currently CFO GSK Consumer Healthcare will be CFO.

Separation rights

As stated above the proposed transaction is transformational to the scale of GSK’s consumer healthcare business and following substantial completion of the integration and further progress in strengthening the pharmaceuticals pipeline, GSK intends to separate the Joint Venture from GSK via a demerger of its equity interest to GSK shareholders and a listing of the GSK Consumer Healthcare business on the UK equity market. This is expected to be within 3 years of the closing of the transaction.

GSK will have the sole right to decide whether and when to initiate a separation and listing for a period of five years from closing of the proposed transaction. GSK has also retained the right to sell all or part of its stake in the Joint Venture in a contemporaneous IPO. In the event of the separation and listing occurring in this period, Pfizer has the option to participate through the demerger of its equity interest in the Joint Venture to its shareholders or the sale of its equity interest in a contemporaneous IPO. After the fifth anniversary of closing of the proposed transaction, both GSK and Pfizer will have the right to decide whether and when to initiate a separation and listing of the Joint Venture.

In circumstances where Pfizer initiates a separation and listing of the Joint Venture after the fifth anniversary of closing of the proposed transaction, GSK will have the right to acquire all (but not part) of Pfizer’s equity interest in the Joint Venture at fair market value. In addition, from the fifteenth anniversary of closing of the proposed transaction, GSK will have the right to acquire all (but not part) of Pfizer’s equity interest in the Joint Venture at fair market value.

As a part of any separation and listing, the Joint Venture will incur borrowings so as to result in an initial ratio of net debt to the aggregate of the Joint Venture’s last four quarters’ Adjusted EBITDA of between 3.5x and 4.0x. The cash proceeds of this recapitalisation will be distributed by the Joint Venture to GSK and Pfizer in proportion to their respective interests in the Joint Venture prior to any separation and listing.

In the event of any separation and listing, GSK also has the right to determine the Joint Venture’s prospective dividend policy provided the pay-out ratio is between 30% and 50% of the aggregate of the Joint Venture’s last four quarters’ Adjusted profit attributable to shareholders.

Conditions to closing

Pfizer is treated as a related party of GSK for the purposes of the UK Listing Rules by virtue of its interest in ViiV Healthcare and, as such, the proposed transaction is conditional upon the approval of GSK’s shareholders at a general meeting. GSK has agreed that its Board will recommend that shareholders vote in favour of the resolution approving the Proposed Transaction, subject to provisions that allow the recommendation to be withdrawn on account of fiduciary duties. The proposed transaction is also conditional on there being no governmental orders restraining or prohibiting the transaction and certain anti-trust authority approvals.

Expected timetable to closing

A circular setting out further details on the proposed transaction, including the resolution seeking shareholder approval, will be sent to GSK shareholders in the first quarter of 2019. Closing of the proposed transaction is currently expected to occur during the second half of 2019, subject to shareholder approval and relevant anti-trust approvals.

Break fee

GSK has agreed to pay a break fee of US$900 million if (i) the Board changes, withdraws or qualifies its recommendation; (ii) shareholders vote on the proposed transaction and do not approve it; or (iii) shareholders do not approve the proposed transaction by 30 September 2019 (or, at either GSK’s or Pfizer’s option, 31 December 2019 or 31 March 2020 in the case of delayed anti-trust approvals).

By virtue of Pfizer being a related party of GSK under the UK Listing Rules, the break fee constitutes a smaller related party transaction within LR11.1.10R of the UK Listing Rules. GSK has obtained written confirmation from Citi and J. P. Morgan Cazenove that the terms of the break fee are fair and reasonable so far as GSK’s shareholders are concerned.

Advisors

GSK has been advised by Citi, who has been acting as lead advisor, J. P. Morgan Cazenove and Greenhill & Co. Slaughter and May and Kirkland & Ellis LLP have provided legal advice.

Advice to the Board

The Board, which has been so advised by Citi and J. P. Morgan Cazenove, considers the terms of the proposed transaction to be fair and reasonable so far as shareholders are concerned. In providing their advice to the Board, Citi and J. P. Morgan Cazenove have taken into account the Board’s commercial assessment of the proposed transaction.

Information on GSK’s consumer healthcare business

As at 31 December 2017, the value of the gross assets of GSK’s consumer healthcare business to be contributed to the new Joint Venture was £16,071 million. In the financial year ended 31 December 2017, that business had sales of £7,110 million, Adjusted operating profit of £1,254 million, Total operating profit of £891 million and Total profit before tax of £884 million.

Information on Pfizer’s consumer healthcare business

As at 31 December 2017, the value of the gross assets of Pfizer’s consumer healthcare business to be contributed to the new Joint Venture was $10,026 million. In the financial year ended 31 December 2017, that business had sales of $3,469 million, Adjusted operating profit of $600 million, Total operating profit of $471 million and Total profit before tax of $471 million.

Sources of information and bases of calculation

Unless otherwise stated, the financial information in this announcement relating to GSK’s contributed consumer healthcare business is based on the audited consolidated financial statements of GlaxoSmithKline Consumer Healthcare Holdings Limited for the year ended 31 December 2017 (from which Novartis was bought out in June 2018), which were prepared under IFRS, adjusted for the perimeter changes that GSK will make to the business contributed to the new Joint Venture, and that relating to Pfizer’s contributed consumer healthcare business is extracted from carve out accounts prepared by Pfizer under US GAAP, adjusted to exclude certain items that were allocated to the business by Pfizer in preparing those accounts but which are not within the perimeter of the business being contributed to the new Joint Venture. Figures in respect of the combined sales of the new Joint Venture have been calculated by aggregating the 2017 sales of GSK’s consumer healthcare business, prepared under IFRS, and the 2017 sales of Pfizer’s consumer healthcare business, prepared under US GAAP; no reconciliation from US GAAP to IFRS has been performed. Conversions use an exchange rate of £1=US$1.30, being the average exchange rate for 2017.

GSK uses a number of adjusted, non-IFRS, measures to report the performance of its business, as described on page 37 of GSK’s Q3 2018 results, including Adjusted results, free cash flow and CER growth rates. Financial information in this announcement relating to Pfizer is presented on a similar basis. Non-IFRS measures may be considered in addition to, but not as a substitute for or superior to, information presented in accordance with IFRS.

This announcement contains inside information for the purposes of Article 7 of EU Regulation 596/2014. The person responsible for arranging the release of this announcement on behalf of GSK is V.A. Whyte, Company Secretary.

INmune Bio Granted Phase I Clinical Trial Authorization of Lead Product INKmune™ in Refractory and Recurrent Ovarian Cancer Patients

On December 19, 2018 INmune Bio Inc., an immunotherapy company developing treatments to reprogram the innate immune system to fight disease, reported that it has been granted Clinical Trial Authorization (CTA) by the United Kingdom (UK) regulatory authority, Medicines and Healthcare products Regulatory Agency (MHRA), for a Phase I clinical trial of its lead therapeutic candidate INKmune (Press release, INmune Bio, DEC 19, 2018, View Source [SID1234532170]). The innate immune drug will be used to treat relapsed and refractory ovarian cancer in a UK based trial.

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"The CTA approval for the first clinical trial of INKmune is a major milestone for the company," said RJ Tesi, M.D, chief executive officer and co-founder of INmune Bio. "INKmune is our second cancer program to enter the clinic and will be tested in women with relapsed and refractory ovarian cancer, which accounts for more deaths than any other cancer of the female reproductive system."

Modern cancer therapy strives to harness the patient’s immune system to help control the cancer. Natural killer (NK) cells of the innate immune system must function normally to eliminate residual disease – the cancer left over after traditional cancer therapy that is the cause of cancer relapse. INKmune is a novel cancer therapy that may switch on the patient’s NK cells to attack residual disease that can be the cause of treatment failure.

"This approval represents external validation of our pre-clinical data set using Tumor Primed NK cells against a range of cancer cells which are insensitive to NK killing," says Dr. Mark Lowdell, chief scientific officer and co-founder of INmune Bio. "The way that INKmune activates the patient’s own immune system means that it could be used for many types of cancer; women with ovarian cancer are just the first of many patients we hope to treat with INKmune."

Today, ovarian cancer ranks fifth in cancer deaths among women. In 2018 alone, the American Cancer Society estimated 22,240 new cases in the US. Unfortunately, when ovarian cancer relapse occurs, the average survival is between 12 to 18 months, and fewer than 1 in 10 patients survive beyond five years following standard chemotherapy treatment.

G1 Therapeutics Announces Positive Topline Results from Randomized Phase 2 Trial of Trilaciclib Showing Multi-Lineage Myelopreservation Benefits in 2nd-/3rd-Line Small Cell Lung Cancer

On December 19, 2018 G1 Therapeutics, Inc. (Nasdaq: GTHX), a clinical-stage oncology company, reported positive topline data showing multi-lineage myelopreservation benefits in its randomized, double-blind, placebo-controlled Phase 2 trial evaluating trilaciclib in combination with topotecan as a treatment for 2nd-/3rd-line small cell lung cancer (2/3L SCLC) (Press release, G1 Therapeutics, DEC 19, 2018, View Source [SID1234532167]).

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"This is the third positive Phase 2 trial of trilaciclib in small cell lung cancer showing significant reductions in the duration and occurrence of Grade 4 neutropenia, and lower rates of G-CSF administrations and red blood cell transfusions. Small cell lung cancer is difficult to treat, particularly in later lines of therapy, and trilaciclib has shown potential to improve outcomes for these patients," said Raj Malik, M.D., Chief Medical Officer and Senior Vice President, R&D. "We now have four randomized Phase 2 trials showing trilaciclib’s multi-lineage myelopreservation benefits. We plan to meet with U.S. and European regulatory authorities in 2019 to discuss the totality of trilaciclib data and pathways to approval."

Trial Design

The Phase 1 dose finding portion of this trial enrolled 32 patients. The randomized, double-blind, placebo-controlled Phase 2 portion of the trial enrolled 91 patients with SCLC who had received 1-2 prior lines of therapy. In the three-arm trial, all patients received a chemotherapy regimen of topotecan. Patients were randomized to receive topotecan (1.5 mg/m2) + placebo, or one of two approved doses of topotecan (1.5 mg/m2 or 0.75 mg/m2) + trilaciclib (240 mg/m2). Treatment for all three arms was administered intravenously on Days 1 through 5 of a 21-day cycle.

The standard therapeutic dose of topotecan is 1.5 mg/m2; the 0.75 mg/m2 dose was also included in this trial in order to define the appropriate combination regimen of topotecan and trilaciclib. There were no unexpected safety signals observed at either topotecan dose level. It was determined that 1.5 mg/m2 is the appropriate dose of topotecan when administered in combination with trilaciclib, and key trial findings reported below compare the 1.5 mg/m2 topotecan + placebo arm to the 1.5 mg/m2 topotecan + trilaciclib arm. Data are presented from the intent-to-treat population, with the exception of response rate which is based on the response-evaluable population.

Key Trial Findings

Data from this trial demonstrated that trilaciclib reduced clinically relevant consequences of myelosuppression versus placebo when administered in combination with topotecan.

Achieved both primary endpoints after multiplicity adjustment: the trilaciclib arm demonstrated statistically significant reductions in both the duration of Grade 4 neutropenia in cycle 1 (mean 8 days vs. 2 days; adjusted 1-sided p < 0.0001) and occurrence of Grade 4 neutropenia (75.9% vs. 40.6%; adjusted 1-sided p=0.0160) compared to the placebo arm.

There were seven events of febrile neutropenia (five patients) in the placebo arm compared to two events of febrile neutropenia (two patients) in the trilaciclib arm.

The total number of patients receiving G-CSF was similar between the placebo (n=19/29, 65.5%) and trilaciclib (n=16/32, 50.0%) arms. Trilaciclib treatment resulted in a 45.0% reduction in number of G-CSF administrations per cycle compared to placebo (G-CSF/cycles of chemotherapy: placebo: 66/112; trilaciclib: 44/136).

The total number of patients requiring RBC transfusions (on/after week 5) was similar between the placebo (n=12/29, 41.4%) and trilaciclib (n=10/32, 31.3%) arms. Trilaciclib treatment resulted in a 58.7% reduction in number of RBC transfusions (on/after week 5) per week compared to placebo (transfusions/weeks of therapy: placebo: 27/428; trilaciclib: 13/500).

Exposures of topotecan and duration of therapy were comparable across the two groups.

Objective response rate (ORR) (placebo: n=6/26, 23.1%; trilaciclib: n=4/30, 13.3%), clinical benefit rate (CBR) (placebo: n=16/26, 61.5%; trilaciclib: n=18/30, 60.0%) and median progression-free survival (PFS) (placebo: 4.2 months; trilaciclib: 4.2 months; hazard ratio=0.83) were comparable between the two groups. These findings are consistent with historical data1, 2 (ORR: 16.9% and 10.1%; CBR: 61.5% and 73.4%; median PFS: 3.5 and 3.0 months).

Overall survival (OS) data is immature and will be reported when available.

Consistent with previous trilaciclib Phase 2 trials, treatment was well tolerated and there were fewer Grade ³ 4 treatment emergent adverse events (TEAEs) in the trilaciclib arm compared to the placebo arm.

"We have observed positive, multi-lineage myelopreservation benefits across different tumor types, lines of therapy and chemotherapy regimens in four randomized Phase 2 trials," said Mark Velleca, M.D., Ph.D., Chief Executive Officer. "The totality of the data demonstrates trilaciclib’s potential to become a standard of care with chemotherapy and improve patient outcomes."

Webcast and Conference Call

The management team will host a webcast and conference call at 4:30 p.m. ET today to provide an overview of the trial findings and next steps for the trilaciclib development program. The live call may be accessed by dialing 866-763-6020 (domestic) or 210-874-7713 (international) and entering the conference code: 5489226. A live and archived webcast will be available on the Events & Presentations page of the company’s website: www.g1therapeutics.com.

von Pawel et al. J Clin Oncol 2014 32:4012-4019.

Evans et al. J Thorac Oncol 2015; 10: 1221–1228

About Trilaciclib

Trilaciclib is a first-in-class myelopreservation therapy designed to improve outcomes of patients who receive chemotherapy by preserving hematopoietic stem and progenitor cell (HSPC) and immune system function. Trilaciclib is a short-acting intravenous CDK4/6 inhibitor administered prior to chemotherapy.

Trilaciclib is being evaluated in four randomized Phase 2 clinical trials; G1 has reported positive results from all of these trials in 2018. Two trials showed myelopreservation benefits in treatment-naive SCLC patients. In one of the first-line SCLC trials, trilaciclib was administered in combination with a chemotherapy regimen of etoposide and carboplatin (NCT02499770); topline data were released in March and additional data were reported at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress. In another first-line SCLC trial, trilaciclib was administered in combination with the same chemotherapy regimen and the checkpoint inhibitor Tecentriq (atezolizumab) (NCT03041311); topline data were reported in November. Results from a trial in combination with chemotherapy in metastatic triple-negative breast cancer (NCT02978716) showing improved progression-free survival and multi-lineage myelopreservation benefits were presented at the San Antonio Breast Cancer Symposium on December 5, 2018. The company issued a press release announcing positive topline data from a trial in combination with chemotherapy in previously treated SCLC (NCT02514447) on December 19, 2018.