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.

On March 7, 2019 NuCana plc (NASDAQ: NCNA) reported financial results for the fourth quarter and year ended December 31, 2018 and provided an update on its extensive clinical program with its transformative ProTide therapeutics (Press release, Nucana BioPharmaceuticals, MAR 7, 2019, View Source [SID1234534063]).

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As of December 31, 2018, NuCana had cash and cash equivalents of £77.0 million compared to £78.4 million as of September 30, 2018 and £86.7 million as of December 31, 2017. NuCana reported a loss of £3.6 million for the quarter ended December 31, 2018, compared to £5.0 million for the quarter ended December 31, 2017 as the Company continued to advance its various clinical programs. Net loss for the year ended December 31, 2018 was £13.8 million, compared to a net loss of £23.1 million for the year ended December 31, 2017. Basic and diluted loss per share was £0.11 for the quarter and £0.43 for the year ended December 31, 2018, compared to £0.16 per share for the comparable quarter and £0.89 on a year-over-year basis in 2017.

NuCana believes its current cash and cash equivalents will be sufficient to fund operations into 2021. In addition to continuing or completing the ongoing clinical studies, NuCana’s current cash and cash equivalents will enable the following:

Open a Phase III study of Acelarin in combination with cisplatin in patients with advanced or metastatic biliary tract cancer;

Initiate a Phase II/III study of Acelarin in combination with a platinum agent for patients with ovarian cancer; and

Initiate a Phase II/III clinical study of NUC-3373 in combination with other agents for patients with colorectal cancer.

"2018 has been another very productive year for NuCana highlighted by several encouraging clinical data presentations for Acelarin and NUC-3373," said Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer. "We began the year by announcing interim data at ASCO (Free ASCO Whitepaper)-GI from the ongoing Phase Ib study of Acelarin plus cisplatin for patients with advanced biliary tract cancer, which showed a 50% response rate, approximately doubling the response rate seen with the standard of care, gemcitabine plus cisplatin, in this patient population. At the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress in October, we announced that the second cohort from this study maintained a 50% response rate. In addition, results showed the combination was well-tolerated and several patients achieved significant reductions in their tumor volume as well as further tumor shrinkage over time."

Mr. Griffith continued: "Additionally, in October we announced at ESMO (Free ESMO Whitepaper) interim data from an ongoing Phase I study of our second ProTide, NUC-3373, a transformation of the active anti-cancer metabolite of 5-fluorouracil (5-FU), in patients with advanced solid tumors who had exhausted all current standards of care. Notably, three patients achieved stable disease lasting more than nine months at the time of data cutoff and, importantly, no patients developed hand-foot syndrome, which is a debilitating side effect associated with fluoropyrimidine therapy."

Mr. Griffith added: "In addition to the clinical successes of our first two ProTides, we expect to enroll the first patients with advanced solid tumors in the Phase I clinical study of our third ProTide, NUC-7738, which is based on a novel nucleoside analog, 3’-deoxyadenosine, and which has shown potent anti-cancer activity in preclinical studies."

Mr Griffith concluded: "We are very pleased with the progress NuCana made in 2018. We have continued to validate our ProTide technology’s ability to transform some of the most widely prescribed chemotherapy agents into more efficacious and safer treatments. With plans to open a Phase III study of Acelarin plus cisplatin in patients with advanced biliary tract cancer and additional data from the two ongoing studies with NUC-3373, as a single agent in patients with advanced solid tumors as well as in combination with other agents typically combined with 5-FU in patients with advanced colorectal cancer, we anticipate 2019 being another important year for NuCana."

Anticipated Milestones

Acelarin is NuCana’s ProTide transformation of gemcitabine. In 2019, NuCana expects to:

Open a Phase III study of Acelarin combined with cisplatin as a first-line treatment for patients with advanced biliary tract cancer.

Contingent on regulatory guidance and other factors, evaluate the initiation of a Phase II/III study of Acelarin in combination with a platinum agent for patients with ovarian cancer.

Report interim data from the ongoing Phase II study (PRO-105) of single-agent Acelarin for patients with platinum-resistant ovarian cancer.

Continue enrollment in the Phase III study (Acelarate) of Acelarin as a first-line treatment compared to gemcitabine for patients with metastatic pancreatic cancer.

NUC-3373 is NuCana’s second ProTide in clinical development, a transformation of the active anti-cancer metabolite of 5-FU. In 2019, NuCana expects to:

Report interim data from the ongoing Phase Ib study (NuTide:302) of NUC-3373 in patients with advanced colorectal cancer in combination with other agents with which 5-FU is typically combined, including leucovorin, oxaliplatin and irinotecan.

Report additional data from the ongoing Phase I study (NuTide:301) of NUC-3373 in patients with advanced solid tumors.

Contingent on regulatory guidance and other factors, initiate a Phase II/III study of NUC-3373 in combination with other agents for patients with advanced colorectal cancer.

NUC-7738 is NuCana’s ProTide transformation of a novel nucleoside analog, 3’-deoxyadenosine . In 2019, NuCana expects to:

Report interim data from the Phase I study (NuTide:701).

On March 7, 2019 Apellis Pharmaceuticals, Inc., (Nasdaq:APLS) a clinical-stage biopharmaceutical company focused on the development of novel therapeutic compounds to treat disease through the inhibition of the complement system, reported the pricing of its underwritten public offering of 6,000,000 shares of its common stock at a public offering price of $17.00 per share, for total gross proceeds of $102 million, before deducting underwriting discounts and commissions and expenses payable by Apellis (Press release, Apellis Pharmaceuticals, MAR 7, 2019, View Source [SID1234534062]). All of the shares in the offering are being sold by Apellis. In addition, Apellis has granted the underwriters a 30-day option to purchase up to 900,000 additional shares of its common stock at the public offering price, less the underwriting discount and commissions. The offering is expected to close on March 11, 2019, subject to customary closing conditions.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Citigroup, J.P. Morgan and Cowen are acting as joint book-running managers for the offering. Cantor Fitzgerald & Co. is acting as lead manager for the offering.

The shares are being offered by Apellis pursuant to an effective shelf registration statement that was previously filed with the Securities and Exchange Commission ("SEC") on December 28, 2018 and amended on February 26, 2019. This offering is being made only by means of a prospectus and prospectus supplement that form a part of the registration statement. A preliminary prospectus supplement relating to and describing the terms of the offering has been filed with the SEC and may be obtained for free by visiting the SEC’s website at www.sec.gov. A final prospectus supplement relating to the offering will be filed with the SEC. When available, copies of the final prospectus supplement and the accompanying prospectus may also be obtained by contacting: Citigroup Global Markets Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, telephone: 1-800-831-9146; J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, telephone: (866) 803-9204; or Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, telephone: (631) 274-2806.

This press release shall not constitute an offer to sell, or a solicitation of an offer to buy these securities, nor shall there be any sale of, these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On March 7, 2019 BioXcel Therapeutics, Inc. ("BTI" or "Company") (Nasdaq: BTAI), reported quarterly results for the fourth quarter and full year ended December 31, 2018 and provided an update on key strategic and operational initiatives (Press release, BioXcel Therapeutics, MAR 7, 2019, View Source [SID1234534061]). BTI is a clinical-stage biopharmaceutical development company utilizing novel artificial intelligence approaches to identify the next wave of medicines across neuroscience and immuno-oncology.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Fourth Quarter 2018 and Recent Highlights:

(BXCL501)-Neuroscience Program-

·Dosed multiple patient cohorts in the first-in-human pharmacokinetic (bioavailability) and safety study of BXCL501, a novel sublingual thin film formulation of dexmedetomedine (Dex)

·Received FDA Fast Track Designation for BXCL501 for acute treatment of mild to moderate agitation associated with schizophrenia, bipolar disorder, or dementia

·Reported positive proof-of-concept data from two independent Phase 1 studies of intravenously administered Dex with high response rates in Schizophrenia and Alzheimer’s Disease / Dementia, supporting BXCL501 as a potential therapy for acute treatment of agitation in these indications

·Expanded indication for BXCL501 to treat symptoms associated with opioid withdrawal based on positive data from a third Phase 1b study of IV Dex

(BXCL701)-Immuno-Oncology Program-

·Received FDA acceptance of IND for BXCL701, an orally-available systemic innate-immune activator that inhibits dipeptidyl peptidase (DPP) 8/9 and fibroblast activation protein (FAP), for treatment emergent neuroendocrine prostate cancer (tNEPC); patient recruitment ongoing

·Received FDA IND acceptance for clinical trial of BXCL701 in pancreatic cancer to advance understanding of its mechanism of action (MoA); clinical site being activated

·Established clinical partnership with Pfizer and Merck KGaA, Darmstadt, Germany, to evaluate BXCL701 combination therapy in pancreatic cancer, along with Nektar Therapeutics

·Received positive feedback from FDA pre-IND meeting on proposed clinical trial of BXCL701, NKTR-214 and avelumab for treatment of metastatic pancreatic cancer

·Continued to explore additional combination therapy approaches to expand BXCL701’s target indications beyond tNEPC and pancreatic cancer

Emerging Programs-

·Continued to leverage the artificial intelligence platform owned by BioXcel Corporation, BTI’s parent, to select and prioritize additional development opportunities to expand the current portfolio and broaden the addressable market for its lead programs through identification of new indications

Dr. Vimal Mehta, Chief Executive Officer of BTI said, "Following our successful Initial Public Offering we achieved significant clinical, regulatory and operational milestones throughout 2018. Over the last 12 months, we have initiated multiple human clinical trials for BXCL501 and BXCL701, reported positive human proof-of-concept data from several trials, signed new clinical partnerships, significantly advanced Chemistry, Manufacturing and Controls (CMC) work on our lead programs and expanded the addressable markets for these programs. In addition, we are in discussions with a number of highly qualified Board candidates and anticipate appointing a new board member in the near future. As we evolve to a late-clinical-stage organization, we remain confident in the potential of our pipeline assets to generate meaningful clinical benefit for patients in need."

"We dosed multiple patient cohorts in our first-in-human pharmacokinetic (bioavailability) and safety study of BXCL501, and we are on track to report data from this study in the first half of 2019. This data will help establish a foundation to launch registration studies later this year. Additionally, we received FDA Fast Track designation for BXCL501 for the acute treatment of mild to moderate agitation associated with schizophrenia, bipolar disorder, or dementia. This regulatory designation would potentially facilitate the development of BXCL501, allow more frequent meetings and more frequent written communication with the FDA, and expedite its regulatory review.

"In the fourth quarter of 2018, we reported positive data from the Phase 1 studies of Dex for acute treatment of agitation in Schizophrenia and Senile Dementia of the Alzheimer’s Type (SDAT) patients. The positive data from these trials support the continued clinical development of BXCL501 for the acute treatment of agitation in schizophrenia and dementia. We also recently announced positive data from a Phase 1b trial that established the potential application of BXCL501 for the treatment of opioid withdrawal symptoms.

"In our BXCL701 program, we received IND acceptances from the FDA to commence trials in both tNEPC and pancreatic cancer. The Phase 1b trial, which was initiated in late 2018 for tNEPC, will be conducted in combination with pembrolizumab (Keytruda) and will examine safety, pharmacokinetics and anti-tumor activity of the combination therapy. Data from this trial is expected throughout 2019. We also plan to initiate a clinical study to understand the underlying role of BXCL 701 and its mechanism of action in treatment of pancreatic cancer. Pfizer and Merck KGaA recently joined our clinical collaboration with Nektar to advance the triple combination of BXCL701, NKTR-214 and avelumab in this indication. This collaboration reinforces the industry’s enthusiasm around the potential of BXCL701 to treat pancreatic cancer. We believe that our triple combination therapy has the ability to target multiple facets of the disease etiology as well as activate the immune system to produce a clinical benefit in pancreatic cancer patients. We are highly encouraged by this collaboration and look forward to leveraging the regulatory and clinical expertise of our partners as we move forward with our development plans."

Dr. Mehta concluded, "In an effort to further expand the addressable indications for BXCL701, we continue to explore additional combination therapy approaches beyond tNEPC and pancreatic cancer. We are pleased to announce that a recent preclinical study of BXCL701 in combination with an OX40-Agonist was accepted as a late-breaking abstract at the upcoming AACR (Free AACR Whitepaper) Annual Meeting, which we believe demonstrates the broader potential of our lead immuno-oncology candidate beyond tNEPC and pancreatic cancer.

"We are extremely pleased with the substantial progress we have made in advancing both BXCL501 and BXCL701, and believe that our recent achievements have positioned us well for continued growth in 2019 and beyond."

Fourth Quarter & Full Year 2018 Financial Results

BTI reported a net loss of $7.1 million for the fourth quarter of 2018, compared to a net loss of $2.5 million for the same period in 2017.

Research and development expenses were $6.0 million for the fourth quarter of 2018, as compared to $1.4 million for the same period in 2017. The increase was primarily due to an expansion of research and development activities, including increased personnel costs, professional fees, clinical trials, and manufacturing costs associated with BTI’s two lead drug candidates.

General and administrative expenses were $1.3 million for the fourth quarter of 2018, as compared to $1.1 million for the same period in 2017. The increase was primarily due to additional payroll and payroll-related expenses, professional fees and costs associated with operating as a public company.

BTI reported a net loss of $19.3 million for the full year 2018, compared to a net loss of $4.5 million for the same period in 2017.

Research and development expenses were $14.5 million for full year 2018, as compared to $2.7 million for the same period in 2017. The increase was primarily due to an expansion of research and development activities, including increased personnel costs, professional fees, clinical trials, and manufacturing costs associated with BTI’s two lead drug candidates.

General and administrative expenses were $5.4 million for full year 2018, as compared to $1.8 million for the same period in 2017. The increase was primarily due to additional payroll and payroll-related expenses, professional fees and costs associated with operating as a public company.

As of December 31, 2018, cash and cash equivalents totaled $42.6 million.

Upcoming investor conferences:

· 39th Annual Cowen Healthcare Conference — March 11-13, 2019, Boston

· Barclays Global Healthcare Conference — March 12-14, 2019, Miami

· Oppenheimer & Co. 29th Annual Healthcare Conference — March 19-20, 2019, New York City

· H.C. Wainwright Global Life Sciences Conference — April 7-9, 2019, London

· ThinkEquity Conference — May 2, 2019, New York City

· UBS Conference — May 20-22, 2019, New York City

· BMO Capital Markets Prescription for Success Healthcare Conference — May 25, 2019, New York City

About BXCL501:

BXCL501 is a first in class, sublingual film of dexmedetomidine, a selective alpha 2a receptor agonist for the treatment of acute agitation. BTI believes that BXCL501 directly targets a causal agitation mechanism and has demonstrated anti-agitation effects in preclinical and clinical studies. It has a well-established regulatory and reimbursement path in schizophrenia and bipolar disorder, as demonstrated by a previously-approved drug, Adasuve.

About BXCL701:

BXCL701 is a first in class oral immunotherapy with dual mechanisms of action, with an established safety profile from 700 healthy subjects and cancer patients. Designed to stimulate both the innate and acquired immune systems, BXCL701 works by inhibiting dipeptidyl peptidase (DPP) 8/9 and blocking immune evasion by targeting fibroblast activation protein (FAP). Preclinical combination data evaluating BXCL701, a checkpoint inhibitor and other IO agents has demonstrated encouraging anti-tumor activity in multiple tumor types and formation of functional immunological memory. It is under development for tNEPC and pancreatic cancer.