On March 7, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported the submission of a supplemental New Drug Application to the US Food and Drug Administration (FDA) for Venclexta (venetoclax) in combination with Gazyva (obinutuzumab) in people with previously untreated chronic lymphocytic leukaemia (CLL) and co-existing medical conditions (Press release, Hoffmann-La Roche, MAR 7, 2019, View Source [SID1234534072]). The FDA is reviewing the application under the Real-Time Oncology Review pilot programme, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.

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"More than 20,000 people will be diagnosed with untreated chronic lymphocytic leukaemia in the US this year, and many are ineligible for intensive chemotherapy-based options," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We are encouraged that this chemotherapy-free, fixed-duration combination is being reviewed under the FDA’s Real-Time Oncology Review pilot programme, and we are working closely with the agency to bring this new option to people with previously untreated chronic lymphocytic leukaemia as quickly as possible."

Breakthrough Therapy Designation was granted based on results of the randomised phase III CLL14 study, evaluating the fixed-duration combination of Venclexta plus Gazyva, compared to Gazyva plus chlorambucil, in people with previously untreated CLL and co-existing medical conditions. The study met its primary endpoint and showed a statistically significant reduction in the risk of disease worsening or death (progression-free survival [PFS] as assessed by investigator) compared to standard-of-care Gazyva plus chlorambucil. Safety for the Venclexta plus Gazyva combination appeared consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination. Data from the CLL14 study will be presented at an upcoming medical meeting. The CLL14 study is being conducted in cooperation with the German CLL Study Group (GCLLSG), headed by Michael Hallek, MD, University of Cologne.

Venclexta is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the US and commercialised by AbbVie, under the brand name Venclyxto, outside of the US.

About the CLL14 study
CLL14 (NCT02242942) is a randomised phase III study evaluating the combination of fixed-duration Venclexta plus Gazyva compared to Gazyva plus chlorambucil in patients with previously untreated chronic lymphocytic leukaemia (CLL) and co-existing medical conditions. 432 patients with previously untreated CLL were randomly assigned to receive either a 12-month duration of Venclexta alongside six-month duration of Gazyva (Arm A) or six-month duration of Gazyva plus chlorambucil followed by an additional six-month duration of chlorambucil (Arm B). The primary endpoint of the study is investigator-assessed progression-free survival (PFS). Secondary endpoints include PFS assessed by independent review committee (IRC), minimal residual disease (MRD) status, overall response (OR), complete response (with or without complete blood count recovery, CR/CRi), overall survival (OS), duration of response (DOR), event-free survival (EFS), time to next CLL treatment (TTNT), and safety. The CLL14 study is being conducted in cooperation with the German CLL Study Group (GCLLSG), headed by Michael Hallek, MD, University of Cologne.

About Venclexta/Venclyxto (venetoclax)
Venclexta/Venclyxto is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumours, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta/Venclyxto blocks the BCL-2 protein and works to restore the process of apoptosis.

Venclexta/Venclyxto is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the US and commercialised by AbbVie, under the brand name Venclyxto, outside of the US. Together, the companies are committed to research with Venclexta, which is currently being studied in clinical trials across several types of blood and other cancers.

In the US, Venclexta has been granted five Breakthrough Therapy Designations by the FDA: in combination with Gazyva for people with previously untreated chronic lymphocytic leukaemia (CLL) and co-existing medical conditions; in combination with Rituxan for people with relapsed or refractory CLL; as a monotherapy for people with relapsed or refractory CLL with 17p deletion; in combination with hypomethylating agents (azacitidine or decitabine) for people with untreated acute myeloid leukaemia (AML) ineligible for intensive chemotherapy; and in combination with low-dose cytarabine for people with untreated AML ineligible for intensive chemotherapy.

About Gazyva (obinutuzumab)
Gazyva is an engineered monoclonal antibody designed to attach to CD20, a protein expressed on certain B cells, but not on stem cells or plasma cells. Gazyva is designed to attack and destroy targeted B-cells both directly and together with the body’s immune system. Gazyva is marketed as Gazyvaro in the EU and Switzerland.

Gazyva/Gazyvaro is currently approved in more than 90 countries in combination with chlorambucil for people with previously untreated chronic lymphocytic leukaemia, in more than 80 countries in combination with bendamustine for people with certain types of previously treated follicular lymphoma and in more than 70 countries in combination with chemotherapy for previously untreated follicular lymphoma.

Additional combination studies investigating Gazyva/Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.

About the German CLL Study Group (GCLLSG)
Founded in 1996 and headed by Michael Hallek, MD, the GCLLSG has been running various phase III, phase II and phase I trials in chronic lymphocytic leukaemia (CLL) with the goal to provide optimal treatment to patients suffering from this disease. Among those were landmark trials like the CLL8 and the CLL11 trials which led to the current standard of care in CLL. For many years, GCLLSG has been aiming to improve not just the treatment of younger and physically fit patients, but also that of elderly and less fit patients. These patients are generally underrepresented in clinical trials although they constitute the majority of CLL patients treated by doctors in daily practice. The GCLLSG is an independent non-profit research organisation supported by the German Cancer Aid (Deutsche Krebshilfe) www.dcllsg.de.

About Roche in haematology
For more than 20 years, Roche has been developing medicines that redefine treatment in haematology. Today, we are investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. In addition to approved medicines MabThera/Rituxan (rituximab), Gazyva/Gazyvaro (obinutuzumab), and Venclexta/Venclyxto (venetoclax) in collaboration with AbbVie, Roche’s pipeline of investigational haematology medicines includes Tecentriq (atezolizumab), an anti-CD79b antibody drug conjugate (polatuzumab vedotin/RG7596) and a small molecule which inhibits the interaction of MDM2 with p53 (idasanutlin/RG7388). Roche’s dedication to developing novel molecules in haematology expands beyond malignancy, with the development of Hemlibra (emicizumab), a bispecific monoclonal antibody for the treatment of haemophilia A.

On March 7, 2019 Medtronic plc (the "Company") (NYSE:MDT) reported that its wholly-owned subsidiary Medtronic Global Holdings S.C.A. ("Medtronic Luxco") has closed a registered public offering (the "Offering") of €500,000,000 principal amount of Floating Rate Senior Notes due 2021, €1,500,000,000 principal amount of 0.000% Senior Notes due 2021, €1,500,000,000 principal amount of 0.375% Senior Notes due 2023, €1,500,000,000 principal amount of 1.125% Senior Notes due 2027, €1,000,000,000 principal amount of 1.625% Senior Notes due 2031 and €1,000,000,000 principal amount of 2.250% Senior Notes due 2039 (collectively, the "Notes") (Press release, Medtronic, MAR 7, 2019, View Source;p=RssLanding&cat=news&id=2390466 [SID1234534070]). All of Medtronic Luxco’s obligations under the Notes are fully and unconditionally guaranteed by the Company and Medtronic, Inc. ("Medtronic, Inc."), a wholly-owned indirect subsidiary of Medtronic Luxco, on a senior unsecured basis.

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The net proceeds from the Offering will be approximately €6.9 billion, after deducting estimated underwriting discounts and commissions and expenses related to the Offering payable by Medtronic Luxco. The net proceeds of the Offering will be used to fund the previously announced tender offers (the "Tender Offers") for several series of outstanding notes issued by Medtronic, Inc. and Covidien International Finance S.A. ("CIFSA"), a wholly-owned indirect subsidiary of Medtronic plc (together with Medtronic, Inc., the "Offerors"), and to pay accrued and unpaid interest, premiums, fees and expenses in connection with the Tender Offers. Any remaining net proceeds of the Offering will be used for repayment of Medtronic Luxco’s 1.700% senior notes due 2019 at maturity on March 28, 2019 plus accrued and unpaid interest thereon, for payments to be made in connection with the redemption of the Redemption Notes as discussed below and for general corporate purposes.

The Tenders Offers were subject to a financing condition, which condition was satisfied by the closing of the Offering. Following the closing of the Offering, the Offerors accepted for purchase $2.1 billion in aggregate principal amount of the "Any and All Notes" validly tendered and not validly withdrawn on or before 5:00 p.m., New York City time, on March 5, 2019 (the "Early Tender Deadline") and approximately $3.8 billion in aggregate purchase price (excluding accrued and unpaid interest to, but not including, the applicable settlement date and excluding fees and expenses related to the Tender Offers) of the "Maximum Tender Offer Notes" validly tendered and not validly withdrawn on or before the Early Tender Deadline, in each case, in accordance with the press release regarding the pricing terms of the Tender Offers issued on March 6, 2019 (the "Pricing Press Release"). All payments for the Any and All Notes and the Maximum Tender Offer Notes (collectively, the "Tender Offer Notes") purchased in connection with the Early Tender Deadline will also include accrued and unpaid interest on the principal amount of Tender Offer Notes tendered up to, but not including, the early settlement date, which is currently expected to be March 11, 2019.

Although the Tender Offers are scheduled to expire at 12:00 midnight, New York City time, on March 19, 2019 (one minute after 11:59 p.m., New York City time, on March 19, 2019), or any other date and time to which the applicable Offeror extends such Tender Offer, because holders of Maximum Tender Offer Notes subject to the Tender Offers validly tendered and did not validly withdraw Maximum Tender Offer Notes on or prior to the Early Tender Deadline for which the aggregate consideration payable exceeds the Aggregate Maximum Purchase Price, the Offerors do not expect to accept for purchase any tenders of Maximum Tender Offer Notes after the Early Tender Deadline. Holders of Any and All Notes who validly tender such notes following the Early Tender Deadline and at or prior to the applicable expiration date will only receive the applicable Tender Offer Consideration for such Notes accepted for purchase, which is equal to the applicable Total Consideration minus the applicable Early Tender Premium, each as described in the Pricing Press Release.

Today, the Company also announced that it intends to redeem the remaining $0.7 billion in aggregate principal amount of Medtronic, Inc.’s 2.500% Senior Notes due 2020 and $0.2 billion in aggregate principal amount of CIFSA’s 4.20% Senior Notes due 2020 (collectively, the "Redemption Notes") that were not validly tendered on or before the Early Tender Deadline and accepted for purchase, in each case at the redemption prices specified in, and otherwise in accordance with, the indentures governing such Redemption Notes. The redemption date for the Redemption Notes will be April 6, 2019.

Information Relating to the Offering
Barclays Bank PLC and Merrill Lynch International were the joint book-running managers for the Offering. The Offering was made by means of a prospectus and prospectus supplement, copies of which may be obtained for free by visiting EDGAR on the U.S. Securities and Exchange Commission website at www.sec.gov. Alternatively, copies of the prospectus and prospectus supplement for each Offering may be obtained by contacting Barclays Bank PLC, toll free at 1-888-603-5847 and Merrill Lynch International, toll-free at 1-800-294-1322.

Information Relating to the Tender Offers
Barclays Capital Inc. and BofA Merrill Lynch are acting as the dealer managers (the "Dealer Managers") for the Tender Offers. The information agent and tender agent is Global Bondholder Services Corporation ("Global Bondholder"). Copies of the Offer to Purchase and related offering materials are available by contacting Global Bondholder at (866) 470-4200 (U.S. toll-free) or (212) 430-3774 (banks and brokers). Questions regarding the Tender Offers should be directed to Barclays Capital Inc., Liability Management Group at (212) 528-7581 (collect) or (800) 438-3242 (toll free) or BofA Merrill Lynch, Liability Management Group, at (980) 387-3907 (collect) or (888) 292-0070 (toll-free).

None of the Offerors, the Company or their affiliates, their respective boards of directors or managing members, the Dealer Managers, Global Bondholder or the trustee with respect to any series of Tender Offer Notes is making any recommendation as to whether holders of Tender Offer Notes ("Holders") should tender any Tender Offer Notes in response to any of the Tender Offers, and neither the Offerors nor any such other person has authorized any person to make any such recommendation. Holders must make their own decision as to whether to tender any of their Tender Offer Notes, and, if so, the principal amount of Tender Offer Notes to tender.

This press release shall not constitute an offer to sell, a solicitation to buy or an offer to purchase or sell any securities. The Tender Offers are being made only pursuant to the Offer to Purchase and only in such jurisdictions as is permitted under applicable law.

The full details of the Tender Offers, including complete instructions on how to tender Tender Offer Notes, are included in the Offer to Purchase. The Offer to Purchase contains important information that should be read by Holders of Tender Offer Notes before making a decision to tender any Tender Offer Notes. The Offer to Purchase may be downloaded from Global Bondholder’s website at View Source or obtained from Global Bondholder, free of charge, by calling toll-free at (866) 470-4200 (bankers and brokers can call collect at (212) 430-3774).

On March 7, 2019 GTx, Inc. (Nasdaq: GTXI) and Oncternal Therapeutics, Inc., a privately held clinical-stage biotechnology company developing potential first-in-class therapeutic candidates for cancers with critical unmet medical need, reported that they have entered into a definitive merger agreement under which the stockholders of Oncternal would become the majority owners of GTx’s outstanding common stock (Press release, GTx, MAR 7, 2019, View Source [SID1234534068]). The proposed merger will create a publicly-traded, clinical-stage oncology company.

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The combined company will be named Oncternal Therapeutics, Inc. and plans to change its ticker symbol on the Nasdaq Capital Market to ONCT upon closing of the transaction.

The combined company will have a strong balance sheet and deep pipeline of promising oncology drug programs advancing in development:

· Oncternal’s lead program, cirmtuzumab, is an investigational, potential first-in-class anti-ROR1 monoclonal antibody. Cirmtuzumab is currently in a Phase 1/ 2 clinical trial in combination with ibrutinib for the treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). In addition, an investigator-initiated Phase 1 clinical trial of cirmtuzumab in combination with paclitaxel for women with metastatic breast cancer is being conducted at the University of California San Diego (UC San Diego).

·TK216, an investigational, potential first-in-class small molecule designed to inhibit the biological activity of ETS-family transcription factor oncoproteins, is being evaluated alone and in combination with vincristine in a Phase 1 clinical trial in patients with relapsed or refractory Ewing sarcoma.

·A ROR-1 targeted chimeric antigen receptor T-cell (CAR-T) program is in preclinical development at UC San Diego for hematologic and solid tumors.

·A Selective Androgen Receptor Degrader (SARD) program, an investigational, potential first-in-class preclinical program designed for oral administration to treat castration-resistant prostate cancer in men who are non-responsive to current androgen targeted therapies.

Cash, cash equivalents and short-term investments for the combined company are expected to be approximately $26 million, if the merger closes by the end of the second quarter of 2019. These funds are expected to be sufficient to advance Oncternal’s programs into the second quarter of 2020, including the Phase 2 study of cirmtuzumab and ibrutinib, and will fund the planned SARD preclinical studies to support the submission of an investigational new drug application with the U.S. Food and Drug Administration.

James Breitmeyer, MD, PhD, cofounder, president and CEO of Oncternal and a 30-year veteran of the pharmaceutical industry, will continue as president and CEO of the combined company. David Hale, cofounder of Oncternal and a 35-year veteran of numerous successful private and public biotech companies, will continue as Chairman of the Board of the combined company.

"This merger introduces Oncternal and its promising oncology pipeline to the public market and provides additional capital resources to advance our programs to potential value inflection points," said Dr. Breitmeyer. "In addition to clinical data expected from our cirmtuzumab and TK216 programs later this year and during the first half of 2020, we also plan to have preclinical results that get us ready for clinical testing of our ROR1 CAR-T program. The addition of GTx’s SARD technology strengthens our pipeline and augments our entire oncology franchise, which includes a range of therapeutic approaches for a variety of difficult to treat cancers."

"This transaction with Oncternal reflects the continued commitment of our management team and Board of Directors to deliver value to stockholders and make a difference in patients’ lives," said Robert J. Wills, PhD, Executive Chairman of GTx. "Following a thorough review of strategic alternatives, we have determined that a reverse merger with Oncternal will enable GTx investors to participate in Oncternal’s broader pipeline of oncology opportunities, including product candidates designed to address rare disease indications, and enable the continued development of our first-in-class SARD technology by a company whose leadership has deep experience in developing oncology medicines."

About the Proposed Merger

The merger is structured as a stock-for-stock transaction whereby all of Oncternal’s outstanding shares of common stock and securities convertible into or exercisable for Oncternal’s common stock will be converted into GTx common stock and securities convertible into or exercisable for GTx common stock. Immediately following the closing of the transaction, the former stockholders of Oncternal will hold approximately 75% of the outstanding shares of common stock of the combined company. In addition to retaining an ownership interest representing approximately 25% of the outstanding shares of common stock of the combined company, the GTx stockholders of record as of immediately prior to the effective time of the merger will receive non-transferable contingent value rights ("CVR") entitling the holders to receive in the

aggregate 50% of any net proceeds derived from the grant, sale or transfer of rights to SARD or selective androgen receptor modulator (SARM) technology during the term of the CVR and, if applicable, to receive royalties on the sale of any SARD products by the combined company during the term of the CVR. Under certain circumstances further described in the merger agreement, the exchange ratio of the outstanding shares of common stock of the combined company may be adjusted upward or downward based on cash levels of each of the companies at closing.

Upon closing of the transaction, GTx will be renamed Oncternal Therapeutics, Inc. and will be headquartered in San Diego, California under the leadership of Oncternal’s current management team. Although no GTx employee is expected to remain an employee of the combined company, the merger agreement provides that the Board of Directors of the combined company will be comprised of nine members, including seven designated Oncternal directors as well as Robert J. Wills, PhD and Michael G. Carter, MD, from GTx’s current Board. The combined company is expected to trade on The Nasdaq Capital Market under a new ticker symbol, ONCT. The merger agreement has been unanimously approved by the Board of Directors of each company. The transaction is expected to close in the second quarter of 2019, subject to approvals by stockholders of each company and other customary closing conditions.

Aquilo Partners, L.P. is acting as exclusive financial advisor to GTx on the proposed transaction and Cooley LLP serves as legal counsel to GTx. Piper Jaffray is acting as exclusive financial advisor to Oncternal on the proposed transaction and Latham & Watkins, LLP serves as legal counsel to Oncternal.

Conference Call Information

Dr. Wills and Dr. Breitmeyer will co-host a conference call to discuss the proposed merger on March 7, 2019, at 5:30 A.M. Pacific Time at Oncternal’s headquarters in San Diego.

To access the live conference call, please dial 1.877.407.2991 from the U.S. and Canada or 1.201.389.0925 internationally. A playback of the call will be available from approximately 12:00 P.M. Pacific Time today through May 7, 2019 and may be accessed by dialing 877.660.6853 from the U.S. and Canada or 201.612.7415 internationally, and using conference ID 13688553.

The conference call information will also be available on the Investor section of the GTx website at www.gtxinc.com.

On March 7, 2019 Geron Corporation (Nasdaq: GERN) reported financial results for the fourth quarter and full year ended December 31, 2018 and recent events (Press release, Geron, MAR 7, 2019, View Source [SID1234534067]). As of year-end 2018, the Company had approximately $182 million in cash and marketable securities, which is sufficient to commence the planned Phase 3 clinical trial of imetelstat in lower risk myelodysplastic syndromes (MDS) by mid-year 2019.

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"We expect 2019 to be a pivotal year," said John A. Scarlett, M.D., Chairman and Chief Executive Officer. "We are making good progress in the transition of the imetelstat program and expect to assume sponsorship of the imetelstat clinical trials by the end of the second quarter. We continue planning to open the Phase 3 clinical trial of imetelstat in lower risk MDS for enrollment by mid-year, as well as evaluating the potential for late-stage development in MF. In addition, we expect to further expand our team with individuals who have strong development expertise that will enable us to build a robust hematology-oncology franchise."

Recent Events

Building a Development Team with Hematology-Oncology Expertise

The Company recently announced the hiring of two key development executives. Aleksandra Rizo, M.D., Ph.D., the former clinical lead for the imetelstat program at Janssen, joined Geron as Chief Medical Officer. Israel Gutierrez, M.D., who has more than 20 years of oncology clinical development experience, joined Geron as Vice President, Pharmacovigilance and Drug Safety. In addition, Geron plans to open an office in northern New Jersey to access experienced personnel with late-stage hematology-oncology clinical drug development expertise, as well as to enable efficient support for global clinical trials, including the Phase 3 clinical trial of imetelstat in lower risk MDS.

Fourth Quarter 2018 Highlights

IMerge Phase 2 Data Presented Support Initiation of Phase 3 Trial in Lower Risk MDS

Data for the Phase 2 portion of IMerge were presented in an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting on December 2, 2018. Geron believes these data support initiating the Phase 3 portion of IMerge to address an unmet medical need for patients for whom erythropoiesis stimulating agents (ESAs) are not effective and for whom currently available therapies show only modest efficacy, especially in patients with high baseline transfusion burdens who are difficult-to-treat. Lower risk MDS patients in the U.S. represent a large unmet need as there has not been a new drug approved by the Food and Drug Administration (FDA) since 2006.

In the Phase 2 portion of IMerge, 38 patients were enrolled who were transfusion dependent with Low or Intermediate-1 risk non-del(5q) MDS who have relapsed after or are refractory to prior treatment with an ESA and naïve to treatment with a hypomethylating agent (HMA) or lenalidomide. In the trial, transfusion dependence is defined as a patient requiring a minimum of four units of red blood cells (RBC) over a consecutive 8-week time period to treat anemia. The median baseline RBC transfusion burden in the Phase 2 portion of IMerge was eight units per eight weeks, ranging from four to 14 units. The primary efficacy endpoint of the trial is the rate of RBC transfusion-independence (RBC TI) lasting at least eight weeks (8-week RBC TI rate), which is defined as the proportion of patients who are transfusion free for at least eight consecutive weeks since entry into the trial. Key secondary endpoints include durability of response as evidenced through 24-week RBC TI rate and breadth of response through reduction in RBC transfusion burden and rate of RBC transfusions, as well as responses across MDS sub-types.

Primary Efficacy Endpoint:

37% (14/38) of patients achieved an 8-week RBC TI rate
Secondary Efficacy Endpoints:

Durability

26% (10/38) of patients achieved a 24-week RBC TI rate
Transfusion Reduction

The rate of hematologic improvement-erythroid (HI-E) was 71% (27/38), as measured by a reduction of at least four RBC units over eight weeks compared with prior transfusion burden
Mean relative reduction of RBC transfusion burden from baseline was 68%
Broad Clinical Activity Observed

Similar 8-week RBC TI rates were observed in patients with baseline serum erythropoietin (sEPO) levels less than or greater than 500mU/mL
8-week RBC TI rates were also consistent between ringed-sideroblast (RS) positive patients and other patients
The ASH (Free ASH Whitepaper) presentation reported data based on a data cut-off date of October 26, 2018. As of the data cut-off date, the median duration of RBC TI had not been reached. Geron expects more mature data from patients continuing on treatment in the Phase 2 portion of IMerge to be available in 2019 and anticipates submitting such data for presentation at a future medical conference.

IMbark Phase 2 Data Presented Suggest Meaningful Survival Outcome in Relapsed/Refractory MF Patients

Data from the Phase 2 IMbark clinical trial, including new overall survival data, were presented in an oral presentation at ASH (Free ASH Whitepaper) on December 3, 2018.

The IMbark trial evaluated two starting dose levels of imetelstat (either 4.7 mg/kg or 9.4 mg/kg administered by intravenous infusion every three weeks) in more than 100 patients with Intermediate-2 or High-risk myelofibrosis (MF) who were relapsed or refractory to janus kinase inhibitor (JAKi) therapy. To be eligible for enrollment in the IMbark trial, patients had to meet rigorous criteria for having failed or not responded to JAKi treatment, including documented progressive disease during or after JAKi therapy. The ASH (Free ASH Whitepaper) presentation highlighted efficacy and safety data from the trial’s primary analysis, as well as overall survival (OS) data with a clinical cutoff of October 22, 2018 and a median follow up of 27 months.

The ASH (Free ASH Whitepaper) presentation reported that the median OS for the 9.4 mg/kg dosing arm was 29.9 months, which suggests a meaningful survival outcome with imetelstat treatment in this poor-prognosis, relapsed/refractory patient population where there are currently no approved treatments today. Other observational studies of similar patient populations at academic medical centers published recently in medical literature have reported median OS ranges of approximately 12 to 14 months after failure of or discontinuation of ruxolitinib, a JAKi.

Geron plans to discuss the potential for late-stage development of imetelstat in MF with current IMbark investigators, other key opinion leaders (KOLs) and regulatory authorities. The Company expects to facilitate KOL discussions over the coming months. Discussions with regulatory authorities are expected to begin after the investigational new drug (IND) sponsorship has been transferred back to Geron.

The Company plans to outline a decision regarding the potential for future late-stage development in MF by the end of the third quarter of 2019. In making this decision, Geron will conduct an assessment of what would be required to achieve clinical and regulatory success, including the cost and duration of any potential clinical trials.

Imetelstat Safety Results

The safety profile reported in both ASH (Free ASH Whitepaper) presentations for imetelstat-treated patients was consistent with prior clinical trials of imetelstat in hematologic malignancies, and no new safety signals were identified. Cytopenias, particularly neutropenia and thrombocytopenia, were the most frequently reported adverse events, which were predictable, manageable and reversible.

Fourth Quarter and Year-End 2018 Results

For the fourth quarter of 2018, the company reported a net loss of $7.3 million, or $0.04 per share, compared to $7.4 million, or $0.05 per share, for the comparable 2017 period. For 2018, the company reported a net loss of $27.0 million, or $0.15 per share, compared to $27.9 million, or $0.18 per share, for 2017.

Revenues for the fourth quarter of 2018 were $375,000 compared to $191,000 for the comparable 2017 period. Revenues for 2018 and 2017 were each $1.1 million and included royalty and license fee revenues under various non-imetelstat license agreements. The Company adopted a new revenue recognition accounting standard as of January 1, 2018 using the modified retrospective transition method. Revenue for 2018 is presented under the new accounting standard, but revenue for 2017 has not been adjusted and continues to be reported under accounting standards used historically. Therefore, there is a lack of comparability between the periods presented. However, the Company does not expect the adoption of the new revenue recognition accounting standard to have a material impact to its financial statements on an ongoing basis.

Total operating expenses for the fourth quarter of 2018 were $10.0 million compared to $8.0 million for the comparable 2017 period. Total operating expenses for 2018 were $32.1 million compared to $30.3 million for 2017.

Research and development expenses for the fourth quarter of 2018 were $5.1 million compared to $2.5 million for the comparable 2017 period. Research and development expenses for 2018 were $13.4 million compared to $11.0 million for 2017. The increase in research and development expenses for the fourth quarter and year-to-date 2018 periods compared to comparable 2017 periods primarily reflects increases in Geron’s share of imetelstat development costs under the former collaboration agreement with Janssen Biotech, Inc. (Janssen) where Geron’s share increased from 50% to 100% as of the termination date of the collaboration agreement and additional costs for the contract research organization (CRO) and other consultants for the transition of the imetelstat program from Janssen to Geron.

General and administrative expenses for the fourth quarter of 2018 were $4.9 million compared to $5.5 million for the comparable 2017 period. General and administrative expenses for 2018 were $18.7 million compared to $19.3 million for 2017. The decrease in general and administrative expenses in 2018 compared to 2017 primarily reflects the net result of reduced personnel related expenses, including lower stock-based compensation expense, partially offset by higher consulting expenses and higher patent legal expenses with the termination of the imetelstat collaboration with Janssen, as imetelstat patent costs previously were being shared by the two companies on a 50/50 basis.

Interest and other income for the fourth quarter of 2018 was $1.1 million compared to $375,000 for the comparable 2017 period. Interest and other income for 2018 was $3.3 million compared to $1.4 million for 2017. The increase in interest and other income for 2018 compared to 2017 primarily reflects higher yields on the Company’s marketable securities portfolio.

Planned 2019 Activities and Milestones

Geron’s plans for 2019 primarily focus on advancing imetelstat development. The Company believes building a development team with hematology-oncology expertise is essential to executing the Phase 3 clinical trial in lower risk MDS and evaluating the potential for late-stage development in MF, as well as in the future, exploring additional indications for imetelstat and being able to pursue other innovative therapeutics in hematology-oncology. Geron expects the following activities and milestones to occur in 2019:

Transition of Imetelstat Development Program

Complete the transfer of the IND back to Geron by the end of the second quarter.

Complete the transfer of the imetelstat clinical development program back to Geron by the end of the third quarter.

Actively recruit highly-experienced personnel with drug development expertise in myeloid malignancies.
MDS Development

Commence screening and enrollment for the Phase 3 portion of IMerge by mid-year.

Present more mature data from patients in the Phase 2 portion of IMerge at a medical conference.
MF Development

Conduct discussions with IMbark investigators, other MF KOLs and regulatory authorities to identify and consider potential late-stage clinical development plans for relapsed/refractory MF patients.

Outline decision regarding the potential for late-stage development of imetelstat in MF by the end of the third quarter.
Projected 2019 Financial Guidance

The Company expects its operating expenses to increase as it assumes full responsibility for the development and potential commercialization of imetelstat. For fiscal year 2019, the Company expects its operating expense burn to range from $65 to $70 million, of which approximately $10 to $15 million represents one-time costs, such as imetelstat program transition activities from Janssen to Geron, including the transfer of the IND sponsorship, and purchase of raw materials and other supplies in preparation for new drug manufacturing. In addition to the one-time costs, projected 2019 operating expense guidance includes costs for the expansion of the internal development team, the global Phase 3 clinical trial in MDS and the opening of the New Jersey office. The Company plans to grow to a total of approximately 30 to 40 employees by year-end 2019, of which half will be research and development personnel.

Conference Call

Geron will host a conference call to discuss fourth quarter and full year financial results and recent events at 4:30 p.m. ET on Thursday, March 7, 2019.

Participants may access the conference call live via telephone by dialing domestically +1 (877) 303-9139 or internationally +1 (760) 536-5195. The conference ID is 6771719. A live, listen-only webcast will also be available on the Company’s website at www.geron.com/investors/events. If you are unable to listen to the live call, an archived webcast will be available on the Company’s website for 30 days.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Early clinical data suggest imetelstat may have disease-modifying activity through the suppression of malignant progenitor cell clone proliferation, which allows potential recovery of normal hematopoiesis. Ongoing clinical studies of imetelstat include a Phase 2/3 trial called IMerge in lower risk myelodysplastic syndromes (MDS) and a Phase 2 trial called IMbark in Intermediate-2 or High-risk myelofibrosis. Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for the treatment of patients with transfusion-dependent anemia due to lower risk MDS who are non-del(5q) and refractory or resistant to an erythroid stimulating agent.

On March 7, 2019 Zai Lab Limited ("Zai lab" or the Company) (NASDAQ: ZLAB), a China and US-based innovative commercial stage biopharmaceutical company, reported financial results for the full year 2018 and provided a corporate update (Press release, Zai Laboratory, MAR 7, 2019, View Source [SID1234534064]).

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"2018 was a year of rapid evolution toward our goal of becoming a fully integrated global biopharma company," said Dr. Samantha Du, Founder and Chief Executive Officer of Zai Lab. "We became a commercial-stage company with the marketing approvals and launches of ZEJULA and Optune in Hong Kong. In China, niraparib’s NDA submission was accepted more than one year ahead of anticipated timeline, and was granted priority review status by the NMPA. We are very excited to prepare for a potential launch as anticipated in the second half of 2019. Pending the outcome of our clinical trial waiver request with the NMPA, Optune could also be launched in China this year."

"Our assets have demonstrated significant momentum both from advances in our clinical trials in China, which are highlighted below, as well as clinical developments announced by our partners, most recently by MacroGenics for the positive results from their pivotal SOPHIA study. Our broad, late stage pipeline has been carefully constructed to address significant unmet medical needs through products with first-in-class and/or best-in-class profile. We are also building a discovery pipeline that we believe will be synergistic with our clinical portfolio, and we expect to announce one to two IND filings per year starting next year."

Recent Pipeline and Product Highlights

ZL-2306 (niraparib)

In January 2019, Zai Lab announced that the Center for Drug Evaluation of China’s National Medical Products Administration (NMPA) has granted priority review status to the New Drug Application (NDA) for niraparib for the maintenance treatment of adult patients with recurrent epithelial, ovarian, fallopian tube or primary peritoneal ovarian cancer who are in a complete or partial response to platinum-based chemotherapy. NMPA acceptance of the NDA was over one year ahead of expectations. Niraparib was also designated as a "National Science and Technology Major Project" by the Chinese government as part of a key initiative to strengthen local innovation.

In January 2019, Zai Lab announced that it completed patient enrollment of its Phase 3 clinical trial of niraparib, which is in development for second-line maintenance therapy in patients with recurrent platinum-sensitive ovarian cancer.

In October 2018, Zai Lab announced the marketing approval of ZEJULA (niraparib) in Hong Kong for the maintenance treatment of adult patients with recurrent platinum-sensitive high-grade serous epithelial ovarian cancer. The product was launched in Hong Kong in November 2018.

In September 2018, Zai Lab presented results of its clinical trial that evaluated the Pharmacokinetic (PK) profile of niraparib made in China for Chinese ovarian cancer patients. The study demonstrated a comparable PK profile to that generated in the global study conducted by Tesaro (now part of GSK).

In August 2018, Zai Lab dosed its first patient in a Phase 3 registrational trial in China for SCLC (Small-Cell Lung Cancer). Current enrollment is on schedule.

In June 2018, Zai Lab dosed its first patient in a Phase 3 clinical trial in China for first-line maintenance therapy of patients with platinum-responsive ovarian cancer. Current enrollment is on schedule.

Optune (TTFields)

In December 2018, Zai Lab launched Optune in Hong Kong and treated its first patient with newly diagnosed glioblastoma multiforme.

In September 2018, Zai Lab announced a global strategic development collaboration with Novocure. Zai Lab obtained an exclusive license to develop and commercialize TTFields in greater China and will also support enrollment of Chinese patients to accelerate clinical trial enrollment for additional indications.

MacroGenics exclusive collaboration and license agreement

In February 2019, MacroGenics announced positive top-line results from its SOPHIA Phase 3 clinical trial. Margetuximab demonstrated improved progression-free survival compared to HERCEPTIN (trastuzumab) when used in combination with chemotherapy in patients with HER2-positive metastatic breast cancer. We plan to discuss the approval pathway for HER2-positive breast cancer in China with the NMPA.

In November 2018, Zai Lab and MacroGenics entered in to an exclusive collaboration and licensing agreement to develop and commercialize three assets for greater China including: (i) margetuximab, an immune-optimized anti-HER2 antibody; (ii) MGD013, a first-in-class bispecific DART antibody designed to coordinate PD-1 and LAG-3 blockade for the treatment of solid and hematological tumors; and (iii) an undisclosed tri-specific TRIDENT molecule.

ZL-2301 (brivanib)

In September 2018, Zai Lab presented interim results of a Phase 2 clinical trial of brivanib in Chinese patients with previously-treated liver cancer at the Chinese Society of Clinical Oncology. The study demonstrated evidence of anti-tumor activity with a manageable safety profile. Zai Lab plans to conduct a combination study with a PD-1 antibody for HCC patients in China.

FPA 144 (bemarituzumab)

In October 2018, Zai Lab and Five Prime Therapeutics dosed the first patient in a Phase 3 global registrational trial of bemarituzumab in combination with chemotherapy in patients with previously-untreated advanced gastric cancer. The first global patient was dosed at a participating site in China, which was an industry first.

ZL-2401 (omadacycline)

In December 2018, Zai Lab initiated the abbreviated bridging program previously agreed to with the NMPA, which is expected to allow us to significantly accelerate NDA preparation and submission timeline by up to two years

In October 2018, the U.S. FDA approved NUZYRA (omadacycline) for the treatment of adults with community-acquired bacterial pneumonia and acute skin and skin structure infections. The European Medicines Agency also announced acceptance of European Marketing Authorization Application for both oral and intravenous formulations.

ETX2514

ETX2514 is expected to initiate global Phase 3 registrational clinical trials for patients with MDR Acinetobacter pneumonia and bloodstream infections in 2019. In collaboration with Entasis, Zai Lab has been preparing to submit a clinical trial application to initiate patient dosing in the Asia-Pacific portion of the global registrational trial.

Recent Corporate Developments

Throughout 2018, Zai Lab continued to demonstrate its positioning as the "gateway to China for innovative assets" by completing four strategic partnerships and adding six assets into its pipeline. Zai Lab intends to continue to evaluate opportunities that it believes has products or capabilities that are a strategic or commercial fit with Zai Lab’s current drug candidates and business.

In February 2019, Immuno-Oncology Pioneer, Lieping Chen, M.D., Ph.D., joined Zai Lab’s Scientific Advisory Board (SAB). Dr. Chen will advise Zai Lab as it continues to progress its internally-developed oncology pipeline. In addition to Dr. Chen, other members of Zai Lab’s SAB include Neal Rosen, M.D., Ph.D., Gwen Fyfe, M.D., and Richard Flavell, Ph.D., FRS.

In October 2018, William Lis was appointed to Zai Lab’s Board of Directors. Mr. Lis has over 25 years of biopharmaceutical experience. He served as CEO and a Director of Portola Pharmaceuticals, Inc. from 2010 until 2018. Under his leadership, Portola successfully grew from a discovery stage company to a fully integrated R&D and commercial organization. Prior to Portola, Mr. Lis held executive positions at Scios, Inc. (a Johnson & Johnson company) and Millennium Pharmaceuticals.

In September 2018, Zai Lab appointed industry leader, Tao Fu, as President and Chief Operating Officer and opened an office in San Francisco to serve as its U.S. Headquarters and further strengthen its business development and discovery capabilities. Mr. Fu has been, and continues to be, a member of Zai’s Board of Directors since 2017.

In September 2018, Zai Lab raised gross proceeds of $150 million in a public offering of American Depositary Shares.

In August 2018, Yongjiang Hei, MD, Ph.D., joined Zai Lab as Chief Medical Officer of Oncology, and brings with him over 20 years of global oncology clinical development

experience. Dr. Hei was the Global Development Leader for numerous oncology drugs at Amgen and also served as the Medical Head for Amgen China. Dr. Hei also served as the US Medical Director for Roche, and Senior Global Brand Medical Director and Executive Director in Oncology for Novartis.

In August 2018, Kai-Xian Chen, Ph.D., was appointed to Zai Lab’s Board of Directors. Professor Chen is a globally preeminent scientist widely regarded as a pioneer in the field of interdisciplinary healthcare research and also served as a member of the National Committee of Chinese People’s Political Consultative Conference (CPPCC) from 2007 to 2017.

In June 2018, Dr. William Liang was appointed Chief Commercial Officer. Dr. Liang has over 20 years of experience in the biopharma industry, heading China and regional commercial operations of global companies. Dr. Liang was instrumental in establishing market-leading oncology and other franchises in China for AstraZeneca and Roche, overseeing commercial success of top selling drugs such as Tagrisso, Iressa, Tarceva, MabThera, Herceptin, Avastin and Pegasys.

Zai Lab continues to expand its platform, particularly in R&D and commercial teams. As of March 1, 2019, Zai Lab employed 448 full-time employees, including nearly 60 employees with M.D. or Ph.D. degrees. Currently, approximately 40% and 43% of the Company’s employees are engaged in R&D and commercial activities, respectively.

Anticipated 2019 Milestones

ZL-2306 (niraparib)

PK study presentation at AACR (Free AACR Whitepaper) (American Association for Cancer Research)

Potential China NDA approval and launch

Tesaro (now GSK) to announce top-line PRIMA data in first-line maintenance treatment of ovarian cancer for all comers

Initiate trials in other key indications in China

Complete enrollment of first-line ovarian cancer Phase 3 clinical trial

Optune (TTFields)

Potential China GBM NDA approval and launch

Initiate exploratory trial in China for gastric cancer

Margetuximab

Submission of a biologics license application to the U.S. FDA for HER2-positive metastatic breast cancer by our partner MacroGenics

Initiate global phase 3 registrational trial in combination with a PD-1 antibody for patients with gastric cancer

ZL-2301(brivanib)

Initiate Phase 1/2 study in combination with a PD-1 antibody in HCC patients in mainland China and Hong Kong

ETX2514

Initiate global Phase 3 registrational study with Entasis

ZL-2401 (omadacycline)

NDA preparation and potential submission

Full Year 2018 Financial Results

As of December 31, 2018, cash and cash equivalents and short-term investments totaled $263.3 million which includes the net proceeds from the follow-on offering in September 2018.

R&D expenses were $120.3 million for the year ended December 31, 2018 compared to $39.3 million for the same period in 2017. The increase in R&D expenses was primarily attributable to an increase in upfront licensing fees of $46.8 million from four new strategic partnerships in 2018 (including MacroGenics upfront fees of $25.0 million that were expensed in 2018 and paid in January 2019), ongoing and newly initiated late-stage clinical trials, payroll and payroll-related expenses, and expansion of research efforts to support internal programs.

SG&A expenses were $21.6 million for the year ended December 31, 2018 compared to $12.0 million for the same period in 2017. The increase was primarily due to the increase in payroll and payroll-related expenses due to increased commercial and administrative headcount as Zai Lab expanded its operations.

For the year ended December 31, 2018, Zai Lab reported a net loss of $139.1 million, or net loss per share attributable to common stockholders of $2.64, compared to a net loss of $50.4 million, or net loss per share attributable to common stockholders of $2.32, for the year ended December 31, 2017.

Conference Call and Webcast Information

Zai Lab will host a live conference call and webcast today, March 7, 2019 at 8:30 a.m. EST to review its financial results and provide a general business update.

The live webcast can be accessed by visiting the Investors section of Zai Lab’s website at View Source Please connect at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. Alternatively, please call 866-394-4355 (U.S.); 314-888-4344 (International); 800966253 (Hong Kong) or 4006828609 (China) to listen to the live conference call. The conference ID number for the live call is 6980867. A replay of the webcast will be available for on Zai Lab’s website for two weeks following the live conference call. The conference ID for the replay is 6980867.

Website Information

Zai Lab routinely posts important information for investors on the Investor Relations section of its website, www.zailaboratory.com, as a means of disclosing material non-public information. Accordingly, investors should monitor the Investor Relations section of Zai Lab’s website in addition to following Zai Lab’s press releases, SEC filings and public conference calls and webcasts. The information contained on, or that may be accessed through, Zai Lab’s website is not incorporated by reference into, and is not part of, this document.