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Syros Reports Fourth Quarter and Full Year 2017 Financial Results and Highlights Recent Accomplishments and Anticipated Milestones

On March 12, 2018 Syros Pharmaceuticals (NASDAQ: SYRS), a biopharmaceutical company pioneering the discovery and development of medicines to control the expression of genes, reported financial results for the fourth quarter and year ended December 31, 2017 and provided an update on recent accomplishments and planned upcoming events (Press release, Syros Pharmaceuticals, MAR 12, 2018, View Source [SID1234524704]).

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"2017 was an important year for Syros, marked by clinical and preclinical data for SY-1425 and SY-1365 that lay a clear path forward for the further development of both programs," said Nancy Simonian, M.D., Chief Executive Officer of Syros. "Additionally, our pioneering gene control platform continued to deliver, enabling us to expand our early-stage pipeline in cancer and monogenic diseases and enter into a collaboration with Incyte designed to allow us to benefit patients with diseases beyond our current areas of focus. We built on our strong foundation, adding to the leadership team and fortifying our cash position to fund our planned operations into 2020 and drive SY-1425 and SY-1365 to key value inflection points. As we enter 2018, we believe we are well-positioned to execute on our near-term and long-term goals to achieve our vision of becoming a fully integrated biopharmaceutical company with medicines that provide a profound and durable benefit for patients."

Upcoming Milestones

Syros plans to report clinical data in the fourth quarter of 2018 from a cohort in its ongoing Phase 2 trial evaluating SY-1425 in combination with azacitidine in RARA and IRF8 biomarker-positive newly diagnosed acute myeloid leukemia (AML) patients who are not suitable candidates for standard chemotherapy.
Syros plans to report clinical data in the fourth quarter of 2018 from a pilot cohort in its ongoing Phase 2 trial evaluating SY-1425 in combination with daratumumab in RARA and IRF8 biomarker-positive relapsed or refractory AML and higher-risk myelodysplastic syndrome (MDS) patients.
Syros plans to open expansion cohorts in mid-2018 in its ongoing Phase 1 trial of SY-1365 evaluating it as a single agent and in combination with carboplatin in multiple ovarian cancer patient populations. Based on emerging preclinical data showing anti-tumor activity of SY-1365 in hormone receptor-positive (HR-positive) breast cancer models, the Company announced today that it also plans to add an expansion cohort evaluating SY-1365 in combination with fulvestrant in HR-positive metastatic breast cancer patients who progress after treatment with a CDK4/6 inhibitor plus an aromatase inhibitor.
Syros plans to report clinical data in the fourth quarter of 2018 from the dose escalation portion of its ongoing Phase 1 trial of SY-1365 in advanced solid tumor patients.
Syros plans to select a new development candidate from its preclinical pipeline by the end of 2018.
Recent Platform and Pipeline Highlights

In January 2018, Syros announced that the U.S. Patent and Trademark Office issued two patents covering methods for stratifying patients with AML and MDS for treatment with SY-1425.
In January 2018, Syros announced a clinical supply agreement with Janssen Research and Development. Under the terms of the agreement, Janssen is supplying daratumumab for the combination dosing cohort in biomarker-positive relapsed or refractory AML and higher-risk MDS patients in Syros’ ongoing Phase 2 trial of SY-1425.
In December 2017, Syros presented initial clinical data from its ongoing Phase 2 trial of SY-1425 in biomarker-positive patients with AML and MDS at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, showing biological and clinical activity as a single agent and supporting ongoing development of SY-1425 in combination with other therapies:
Clinical activity was observed in 43% of evaluable relapsed or refractory AML and higher-risk MDS patients, including improvement in blood counts and reductions in bone marrow blasts.
Myeloid differentiation was observed, including the induction of CD38 in 85% of evaluable patients.
SY-1425 generally well-tolerated with chronic, daily dosing with the majority of adverse events being low grade.
In December 2017, Syros presented new preclinical data on SY-1365 at ASH (Free ASH Whitepaper). The data showed anti-tumor activity in leukemia and lymphoma cell lines and in vivo models of AML. Additionally, the data pointed to a potential biomarker of response to SY-1365 and demonstrated synergistic activity with venetoclax, a BCL2 inhibitor, in preclinical AML models.
In December 2017, Syros presented new preclinical data on SY-1365 at the San Antonio Breast Cancer Symposium (SABCS). The data demonstrated anti-tumor activity across a broad panel of breast cancer cell lines and pointed to potential biomarkers of response. Syros also presented on its analysis of regulatory regions of the genome in cancer stem cell-enriched triple negative breast cancer (TNBC) cell lines, which revealed key genes that may be involved in driving disease relapse and metastasis in TNBC and suggest potential new targets for future drug discovery and development.
Recent Corporate Highlights

Syros reported the appointment of Joseph J. Ferra as Chief Financial Officer.
In January 2018, Syros announced the closing of an underwritten public offering of 4,816,753 shares of common stock at a public offering price of $9.55 per share, including the exercise in full by the underwriters of their option to purchase additional shares of common stock. Syros received aggregate gross proceeds of approximately $46 million, before deducting underwriting discounts and commissions and estimated offering expenses. In connection with the offering, Incyte Corporation, exercised its right to purchase shares of Syros common stock directly from the company at the public offering price, in a concurrent private placement, resulting in proceeds of approximately $1.4 million.
In January 2018, Syros announced a global target discovery and validation collaboration with Incyte focused on myeloproliferative neoplasms (MPNs). Under the terms of the agreement, Syros will use its proprietary platform to identify novel therapeutic targets with a focus in MPNs. Incyte has options to obtain exclusive worldwide rights to intellectual property resulting from the collaboration for up to seven validated targets and, upon exercise of its options, will have exclusive worldwide rights to develop and commercialize any therapies under the collaboration that modulate those validated targets. Incyte paid Syros $10 million in upfront cash and purchased a total of $10 million in Syros common stock at a price of $12.61 per share. In addition, Syros could receive up to $54 million from Incyte in target validation and option exercise fees and up to $115 million in potential development, regulatory and commercial milestone payments per target for up to seven validated targets, plus low single-digit royalties on sales of products that result from the collaboration.
In November 2017, Syros announced the appointment of Jeremy P. Springhorn, Ph.D., as Chief Business Officer.
Fourth Quarter 2017 Financial Results

Cash, cash equivalents and marketable securities as of December 31, 2017 were $72.0 million, compared with $83.6 million on December 31, 2016. Cash, cash equivalents and short-term investments as of December 31, 2017 do not include the aggregate gross proceeds of approximately $46 million from Syros’ underwritten public offering of common stock, which closed in February 2018, the $1.4 million in proceeds from the private placement of stock with Incyte concurrent with the public offering, or the $10 million upfront payment and purchase of $10 million in Syros common stock received in January 2018 in connection with entry into the collaboration with Incyte.

For the fourth quarter of 2017, Syros reported a net loss of $15.3 million, or $0.58 per share, compared to a net loss of $11.0 million, or $0.47 per share, for the same period in 2016. Stock-based compensation included in the net loss was $1.3 million for the fourth quarter of 2017, compared to $0.7 million for the same period in 2016.

Research and development (R&D) expenses were $11.8 million for the fourth quarter of 2017, as compared to $8.4 million for the same period in 2016. Stock-based compensation included in R&D expenses was $0.5 million for the fourth quarter of 2017, compared to $0.2 million for the same period in 2016.
General and administrative (G&A) expenses were $3.7 million for the fourth quarter of 2017, as compared to $2.9 million for the same period in 2016. Stock-based compensation included in G&A expenses was $0.8 million for the fourth quarter of 2017, compared to $0.5 million for the same period in 2016.
Full Year 2017 Financial Results

For the full year ended December 31, 2017, net loss was $54.0 million, or $2.13 per share, as compared to a net loss of $47.7 million, or $4.05 per share, for the same period in 2016. Stock based compensation included in the net loss was $4.4 million for the year ended December 31, 2017, compared to $4.2 million for the same period in 2016.

R&D expenses were $41.9 million for the year ended December 31, 2017, as compared to $37.8 million for the same period in 2016. The increase was due to an increase in expenses from third parties that conduct research and development and preclinical activities on our behalf, including an increase in clinical development costs for SY-1425 and SY-1365, offset by a decrease in preclinical development work for SY-1365 as toxicology studies were completed and the Phase 1 clinical trial was initiated. Stock-based compensation included in R&D expenses was $1.7 million for the year ended December 31, 2017, compared to $3.0 million for the same period in 2016.
G&A expenses were $13.9 million for the year ended December 31, 2017, as compared to $10.5 million for the same period in 2016. The increase was largely due to an increase in employee-related costs, including salary, benefits and stock-based compensation, as well as increased consulting, licensing, and professional fees to support the overall growth of the Company. Stock-based compensation included in G&A expenses was $2.7 million for the year ended December 31, 2017, compared to $1.2 million for the same period in 2016.
Financial Guidance

Based on its current plans, Syros believes that its cash, cash equivalents and short-term investments as of December 31, 2017, together with cash received in connection with entry into the collaboration with Incyte and the underwritten public offering and concurrent private placement of common stock that closed in February 2018, will be sufficient to enable it to fund its planned operating expense and capital expenditure requirements into 2020.

IMMUTEP ENTERS INTO CLINICAL TRIAL COLLABORATION AND SUPPLY AGREEMENT WITH MSD

On March 12, 2018 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or the "Company") has reported that it has entered into a clinical trial collaboration and supply agreement with Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the United States and Canada), through a subsidiary, to evaluate the combination of Immutep’s lead immunotherapy product candidate eftilagimod alpha ("efti" or "IMP321") with MSD’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in a new clinical trial that will evaluate the combination in several different solid tumours (Press release, Immutep, MAR 12, 2018, View Source [SID1234524702]).

The planned Phase II clinical trial, referred to as TACTI-002 (Two ACTive Immunotherapies), will evaluate the safety and efficacy of this novel immunotherapy combination in patients with non-small cell lung cancer ("NSCLC"), head and neck cancer, or ovarian cancer. The TACTI-002 clinical trial will be a Phase II, Simon two-stage, non-comparative, open-label, single-arm, multicentre clinical study. Up to 120 patients across the three indications are planned to be treated in medical centres in Europe and the United States with the trial expected to commence in the second half of 2018.

"We are extremely pleased to be collaborating with MSD, one of the world’s leading immuno-oncology companies" said Marc Voigt, CEO of Immutep. "This clinical trial will evaluate a novel combination of two complementary immuno-oncology treatments in three cancer indications simultaneously, which could lead to more rapid drug development subject to successful outcomes. The data generated thus far from our ongoing TACTI-mel clinical trial has supported our hypothesis that there is a compelling therapeutic synergy in administering efti in combination with another immuno-oncology treatment. This new Phase II clinical trial significantly builds on the momentum we are delivering in the evaluation of efti in cancer, with two Phase I clinical trials and now two Phase II clinical trials in our program for 2018."

The trial combines two immuno-oncology treatments with complementary mechanisms of action, analogous to releasing the brakes and pushing the accelerator of the body’s immune system at two different positions in the cancer immunity cycle. Immutep’s efti is a first-in-class antigen presenting cell ("APC") activator which stimulates cancer-fighting T cells, while KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells.

Cellectis Reports 4th Quarter and Full Year 2017 Financial Results

On March 12, 2018 Cellectis (Paris:ALCLS) (NASDAQ:CLLS) (Euronext Growth: ALCLS – Nasdaq: CLLS), a clinical-stage biopharmaceutical company focused on developing immunotherapies based on gene-edited allogeneic CAR T-cells (UCART), reported its results for the three-month period ended December 31, 2017 and for the year ended December 31, 2017 (Press release, Cellectis, MAR 12, 2018, View Source [SID1234524700]).

"I would like to highlight what remarkable progress we made in 2017, by transforming the off-the-shelf CAR T-cell concept into reality. I believe I can say without a doubt that we have only just scratched the surface of what a powerful treatment CAR T-cell therapy represents. 2018 will be a turning point for Cellectis, extending our lead in the allogeneic CAR T-cell field," said André Choulika, Chairman and Chief Executive Officer, Cellectis.

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1 Cash position includes cash, cash equivalents and current financial assets.

Earnings Call Details

Cellectis to hold a conference call for investors on Tuesday, March 13, 2018 at 8 a.m. EDT – 1 p.m. Paris Time. The call will include the company’s fourth quarter 2017 and year-end financial results.

The live dial-in information for the conference call is:

US & Canada only: 877-407-3104

International: 201-493-6792

In addition, a replay of the call will be available for 6 months following the conference by calling 877-660-6853 (Toll Free US & Canada); 201-612-7415 (Toll Free International).

The archived webcast of this event will be available archived for 6 months:

https://78449.themediaframe.com/dataconf/productusers/clls/mediaframe/23530/indexl.html

Cellectis – Therapeutics

UCART19: TALEN gene-edited, allogeneic CAR T-Cell product candidate in ALL patients, exclusively licensed to Servier

Intermediary results from the two Phase I clinical trials of UCART19 were presented by Servier at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Atlanta. UCART19 is an investigational allogeneic anti-CD19 CAR T-cell product candidate, used in adult and pediatric patients with relapsed or refractory (R/R) CD19-positive B-cell acute lymphoblastic leukemia (B-ALL). These first-in-human data demonstrated the safety and tolerability of UCART19, resulting in an 83% complete remission rate across the adult and pediatric patient populations at day 28 post CAR T-cell infusion. Our commercial partner Servier is currently expanding the UCART19 clinical studies in multiple centers in the U.S. and Europe and we are expecting further clinical updates by year-end 2018.

Additional results from the two Phase I clinical trials with UCART19 will be presented on March 21, 2018 during the European society for Blood and Marrow Transplantation (EBMT) Annual Meeting to be held in Lisbon, Portugal.

Successful GMP manufacturing of UCART22, representing already the third allogeneic, off-the-shelf, TALEN gene-edited CAR T-cell campaign after UCART19 and UCART123

UCART22 is currently in GMP manufacturing, expected to yield clinical supplies for the planned Ph1 study in ALL patients. Pending the completion of the manufacturing campaign, Cellectis plans to file an Investigational New Drug (IND) application in the first half of 2018. The UCART22 manufacturing campaign represents already the third consecutive manufacturing campaign of a TALEN gene-edited CAR T-cell campaign after UCART19 and UCART123, positioning Cellectis as a leader in the allogeneic, off-the-shelf CAR T-cell space.

UCART123: Cellectis’ TALEN gene-edited, allogeneic CAR T product candidate in AML and BPDCN Patients

In December 2017, patient enrollment has resumed in both Phase I clinical trials of UCART123 in acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN). On November 6, 2017, Cellectis announced that the U.S. Food and Drug Administration (FDA) has lifted the clinical hold, previously announced on September 4, 2017, on both Phase I trials of UCART123. In connection with the lifting of the clinical hold, Cellectis agreed with the FDA to certain revisions to be implemented in Phase I UCART123 protocols.

Corporate

Cellectis announced on December 4, 2017 the appointments of Ms. Elsy Boglioli to the role of Executive Vice President, Strategy and Corporate Development, and Prof. Stéphane Depil, MD, PhD, to the role of Senior Vice President Research & Development and Chief Medical Officer. Ms. Boglioli’s responsibilities include directing the long-term strategy and current business priorities of Cellectis to ensure that the overall mission of the Company is fulfilled. Ms. Boglioli joins Cellectis from Boston Consulting Group (BCG), where she served as Partner and Managing Director, and leader of BCG’s biotech-focused business in Europe. Prof. Depil’s responsibilities include bringing Cellectis’ product candidates to clinical-stage development, strategic and operational management of all therapeutic activities, and supervising research and development projects for the Company. Prof. Depil continues his academic and research activities as adjunct Professor at Léon Bérard Cancer Center & University Claude Bernard in Lyon, France.

Scientific Publications

A poster has been presented at the Keystone Conference in February 2018, showcasing the high gene-editing efficiency of TALEN. A T-cell was edited using TALEN, to knock out the TCR alpha and beta chain, knock out the B2M molecule, knock in the CAR construct and knock in an NK cell inhibitor. This simultaneous double knock out and double knock in resulted at a 68.1% efficiency.

A study has been published in November 2017 in Molecular Therapy — Nucleic Acids describing the educated engineering of highly specific and efficient TAL nucleases (TALEN) targeting PD1, a key T-cell immune checkpoint.

Upcoming Investor Conferences

Cellectis will participate in Oppenheimer’s 28th Annual Healthcare Conference & Sachs BioCapital USA Forum both on March 21 in New York, and Guggenheim Conference on Disruptive Technologies in Immuno-Oncology on March 27, 2018 in New York.

Calyxt

On December 12, 2017 Calyxt signed a partnership with Farmer’s Business Network, Inc (FBNSM), the independent farmer-to-farmer network, to expand the distribution and grower base of Calyxt’s identity-preserved high oleic soybeans in the upper Midwest region, including South Dakota and Minnesota. This new partnership enables FBN DirectTM to distribute Calyxt’s identity-preserved high oleic soybean seeds to growers in its network.

Calyxt announced on March 1, 2018 having contracted over 10,000 acres with 50 farmers in the Midwest. Overall, these growers collectively farm over 100,000 acres, half of which are expected to produce soybeans. Twenty percent of the soybeans that are anticipated to be planted consist of Calyxt’s high-oleic variety.

Corporate

Initial Public Offering: On July 25, 2017, Calyxt completed an initial public offering of its common stock, selling an aggregate of 8,050,000 shares of common stock at a price of $8.00 per share (including 1,050,000 shares of common stock pursuant to the exercise by the underwriters of their option to purchase additional shares). Calyxt received net proceeds of approximately $58.0 million, after deducting underwriting discounts and commissions and offering expenses. As part of the IPO, Cellectis purchased 2,500,000 shares of common stock for a value of $20.0 million, which is included in the net proceeds that Calyxt received. Calyxt used $5.7 million of the proceeds to cover a portion of the outstanding obligations owed to Cellectis. As of February 28, 2018, Cellectis owns 79.3% of the outstanding Calyxt’s common shares.

Financial Results

Cellectis’ consolidated financial statements have been prepared in accordance with International Financial Reporting Standards, or IFRS, as issued by the International Accounting Standards Board ("GAAP").

Effective in the third quarter of 2017, Cellectis changed the presentation currency of its consolidated financial statements from the euro to the U.S. dollar, in order to enhance comparability with peers, which present their financial statements primarily in U.S. dollar.

Fourth quarter 2017 Financial Results

Cash: As of December 31, 2017, Cellectis had $297.0 million in total cash, cash equivalents and current financial assets compared to $304.1 million as of September 30, 2017. This decrease of $7.1 million reflects (i), the net cash flows used by operating activities of $9.5 million and (ii) net cash provided by investing activities of $0.5 million, partially offset by (iii) the unrealized positive translation effect of exchange rate fluctuations on U.S. dollar cash, cash equivalents and current financial assets of $2.0 million and (iv) net cash flows provided by financing activities of $0.9 due to the exercise of Cellectis warrants and stock options during the period.

Selecta Biosciences Announces First Patient Dosed in Phase 1 Trial of SVP-Rapamycin and LMB-100 Combination Therapy in Mesothelioma

On March 12, 2018 Selecta Biosciences, Inc. (Nasdaq:SELB), a clinical-stage biopharmaceutical company focused on unlocking the full potential of biologic therapies by avoiding unwanted immune responses, reported that the first patient has been dosed in a Phase 1 clinical trial of SEL-403, Selecta’s product candidate consisting of SVP-Rapamycin in combination with LMB-100 (Press release, Selecta Biosciences, MAR 12, 2018, View Source [SID1234524682]). The trial (ClinicalTrials.gov Identifier# NCT03436732 ), is enrolling patients with malignant pleural or peritoneal mesothelioma who have undergone at least one regimen of chemotherapy, and it is being conducted under a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI), part of the National Institutes of Health.

SVP-Rapamycin is Selecta’s proprietary, clinical-stage anti-drug antibody (ADA) prevention and immune tolerance technology. LMB-100 is a recombinant immunotoxin that targets mesothelin, a protein expressed in nearly all mesotheliomas and pancreatic adenocarcinomas, and a high percentage of other malignancies, including lung, breast and ovarian cancers. A paper co-authored by Selecta and researchers at the NCI discussing preclinical work completed with this combination therapy candidate was recently published in Proceedings of the National Academies of Sciences (PNAS, 2018 Jan 23;115(4): E733-E742).

"Mesothelioma remains one of the deadliest and most challenging-to-treat forms of cancer," stated Raffit Hassan, M.D., Senior Investigator, Thoracic and GI Oncology Branch in NCI’s Center for Cancer Research and Principal investigator of the trial. "Recombinant immunotoxins hold the potential to induce marked anti-tumor activity if anti-drug antibodies are prevented and sufficient cycles of therapy can be administered. We are pleased to get this clinical investigation underway to determine if patients may indeed benefit from a combination therapy consisting of LMB-100 and SVP-Rapamycin."

Patients in this open-label dose-escalation trial will receive up to four treatment cycles, each treatment cycle consisting of an initial dose of the combination of SVP-Rapamycin and LMB-100 on day 1 followed by two doses of LMB-100 alone on days 3 and 5. The study, which is expected to enroll up to 18 patients, is designed to evaluate the safety and tolerability of this treatment and provide data on pharmacokinetics, anti-drug antibody (ADA) levels, as well as an objective response rate assessment.

For Patients

Patients interested in enrolling please contact NCI’s toll-free number 1-800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615) and/or the Web site: View Source

About Mesothelioma
Mesothelioma is a mesothelin-expressing cancer predominantly affecting the layer of tissue lining the lungs and chest wall. This type of cancer has been linked to asbestos exposure. According to the American Cancer Society, approximately 3,000 people are diagnosed with this disease each year in the United States. The prognosis for mesothelioma is very poor, with an average life expectancy of 12-18 months following diagnosis.

Portola Pharmaceuticals Announces New Interim Results from Ongoing ANNEXA-4 Study of Factor Xa Inhibitor Reversal Agent AndexXa® (Andexanet Alfa) in Patients with Life-Threatening Bleeding

On March 12, 2018 Portola Pharmaceuticals, Inc. (Nasdaq:PTLA) reported new interim results from ANNEXA-4, the Company’s ongoing Phase 3b/4 trial of its investigational universal Factor Xa inhibitor antidote AndexXa (andexanet alfa) among patients experiencing acute major bleeding while taking a Factor Xa inhibitor (Press release, Portola Pharmaceuticals, MAR 12, 2018, View Source;p=RssLanding&cat=news&id=2337591 [SID1234524680]). Interim data from 228 patients (of which 132 were adjudicated for efficacy) showed that AndexXa rapidly and significantly reversed anti-Factor Xa activity (the anticoagulant mechanism of these drugs) when administered as a bolus, and sustained this reversal when followed by a 120-minute infusion. In addition, 83 percent of these patients achieved excellent or good hemostasis (stoppage of bleeding) over a 12-hour period following treatment with AndexXa. Thrombotic events (11 percent) and death rates (12 percent) were consistent with previous ANNEXA-4 trial results and with the high background thrombotic risk of the enrolled patient population. Results were presented today in a Late-Breaking Clinical Trial Session at the American College of Cardiology’s 67th Annual Scientific Session & Expo (ACC.18).

"These data are particularly compelling when you consider the high-risk profile of the ANNEXA-4 population, which includes a substantial number of elderly patients presenting with intracranial hemorrhage and anticoagulated for venous thromboembolism, and the lack of any FDA- or EMA-approved reversal agent for these patients," said Stuart J. Connolly, M.D., ANNEXA-4 Executive Committee chairman and professor in the Department of Medicine of the Faculty of Health Sciences at McMaster University in Hamilton, Ontario. "The interim efficacy and safety data continue to support the promising role of AndexXa as an antidote to reverse anticoagulation in Factor Xa-associated bleeding."

The use of Factor Xa inhibitors is continuing to grow at a significantly steady pace because of their demonstrated efficacy in preventing embolic diseases such as stroke and pulmonary embolism. However, the incidence of hospital admissions and death related to Factor Xa-inhibitor bleeding is also increasing. In the U.S. alone, there were approximately 117,000 hospital admissions attributable to Factor Xa-related bleeding in 2016 and more than 2,000 bleeding-related deaths per month.

"The ANNEXA-4 trial continues to demonstrate efficacy and safety results that are consistent with that of other therapies approved for anticoagulant reversal based on a single-arm study," said John Curnutte, M.D., Ph.D., executive vice president, research and development at Portola. "We remain confident in the potential of AndexXa to address a clear and growing unmet need and we look forward to sharing these results with the U.S. and European regulatory authorities as they consider our marketing application for andexanet alfa."

The interim results included safety data from 227 of the 228 enrolled patients who experienced intracranial hemorrhage (ICH) (61 percent), gastrointestinal bleeding (27 percent) or bleeding from another site (11 percent) within 18 hours of administration of apixaban (117 patients), rivaroxaban (90 patients), enoxaparin (17 patients) or edoxaban (3 patients). Safety data for the one remaining patient, who was enrolled and active in the study, was not available at the time of this analysis.

During the 30-day follow-up period, the thrombotic event rate was 11 percent (n=24) for the entire population and 12 percent (n=17) among patients experiencing an ICH. The mortality rate for all patients was 12 percent (n=27). The rate of these events occurred within the range expected in this population given the severity of the bleeding, their advanced age and underlying thrombotic risk, and the percentage who restarted anticoagulant therapy (57 percent) following their bleeding episode.

Two of the 228 patients experienced an infusion reaction and none developed antibodies to Factor Xa or Factor X or neutralizing antibodies to AndexXa.

Data from the adjudicated efficacy population of 132 patients, who were confirmed to have major bleeding by the independent adjudication committee, and whose baseline anti-Factor Xa activity was substantially elevated (>75 ng/ml or 0.25 IU/mL if receiving enoxaparin), demonstrate that AndexXa rapidly and substantially reversed anti-Factor Xa activity, and these levels were sustained for the duration of administration.

Specifically, anti-Factor Xa activity, the co-primary efficacy endpoint, decreased by a median of greater than 90 percent for both apixaban and rivaroxaban following the bolus dose, which was sustained at similar levels for the duration of the two-hour infusion.

The independent adjudication committee determined that 109 of 132 patients (83 percent) achieved effective hemostasis, as defined by a hemostatic efficacy rating of "excellent" or "good" (the criteria used by the adjudication committee were based on similar criteria used in a pivotal study of Kcentra, approved for the reversal of Vitamin K antagonists). Among patients with gastrointestinal bleeding, 86 percent had effective hemostasis, as did 81 percent of patients with intracranial bleeding. Hemostatic efficacy was similar for patients on apixaban (82 percent) and rivaroxaban (83 percent).

Portola is developing andexanet alfa as a universal antidote for patients anticoagulated with an oral or injectable Factor Xa inhibitor, including apixaban and rivaroxaban, who experience a serious uncontrolled or life-threatening bleeding event or who require urgent or emergency surgery. Andexanet alfa is currently under review by the U.S. Food and Drug Administration (FDA), with an assigned action date of May 4, 2018, and by the European Medicines Agency (EMA), with an expected decision in 2019.

ANNEXA-4 Study Design
ANNEXA-4 is a global, single-arm, open-label clinical trial designed to evaluate andexanet alfa in patients who present with an acute major bleed while receiving apixaban, rivaroxaban, edoxaban or enoxaparin. This multi-center, prospective cohort study is not randomized and all participants receive andexanet alfa given as a bolus dose over 20-30 minutes followed by a two-hour (120 minute) infusion. Patients receive a low or high dose depending on which Factor Xa inhibitor they have received and the time they received the last dose. Patients are evaluated for 30 days following andexanet alfa administration. The co-primary efficacy endpoints are the maximum percent reduction in anti-Factor Xa activity and assessment of hemostasis over 12 hours following the infusion. Hemostatic efficacy is assessed by an independent endpoint adjudication committee as either excellent, good or poor/none.

Investor Event Webcast Information
Members of Portola’s senior management team, together with Dr. C. Michael Gibson, ANNEXA-4 Executive Committee member, Harvard Medical School professor and chairman of the PERFUSE Study Group, will review these new interim results during a conference call and live audio webcast today at 12:30 p.m. ET (9:30 a.m. PT) following the Late-Breaking Clinical Trial Session.

The conference call can be accessed by phone by calling (844) 452-6828 from the United States and Canada or 1 (765) 507-2588 internationally and using the passcode 8493604. To access the live and subsequently archived webcast, go to the Investor Relations section of the company’s website at View Source A replay will be available for 30 days following the live event.