U.S. FDA Approves Portola Pharmaceuticals’ Andexxa®, First and Only Antidote for the Reversal of Factor Xa Inhibitors

On May 3, 2018 Portola Pharmaceuticals, Inc. (Nasdaq:PTLA) reported that the U.S. Food and Drug Administration (FDA) has approved Andexxa [coagulation factor Xa (recombinant), inactivated-zhzo], the first and only antidote indicated for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding (Press release, Portola Pharmaceuticals, MAY 3, 2018, View Source;p=RssLanding&cat=news&id=2347018 [SID1234526086]).

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Andexxa received both U.S. Orphan Drug and FDA Breakthrough Therapy designations and was approved under the FDA’s Accelerated Approval pathway based on the change from baseline in anti-Factor Xa activity in healthy volunteers. Continued approval for this indication may be contingent upon post-marketing study results to demonstrate an improvement in hemostasis in patients.

"Today’s approval represents a significant step forward in patient care and one that the medical community has been eagerly anticipating," 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. "Andexxa’s rapid reversal of the anticoagulating effects of rivaroxaban and apixaban will help clinicians treat life-threatening bleeds, where every minute counts."

The use of Factor Xa inhibitors is rapidly growing because of their efficacy and safety profile compared to enoxaparin and warfarin in preventing and treating thromboembolic conditions such as stroke, pulmonary embolism and venous thromboembolism (VTE). This growth has come with a related increase in the incidence of hospital admissions and deaths related to bleeding, the major complication of anticoagulation. In the U.S. alone in 2016, there were approximately 117,000 hospital admissions attributable to Factor Xa inhibitor-related bleeding and nearly 2,000 bleeding-related deaths per month.

"We are grateful to the patients who participated in our trials, our clinical trial collaborators, our employees and the FDA for their help in bringing this new drug to market for the benefit of patients with Factor Xa inhibitor-related bleeding," said Bill Lis, chief executive officer of Portola. "We are proud that Andexxa is a first-in-class medicine discovered in our labs. In addition to Bevyxxa, the first and only anticoagulant approved for extended VTE prevention in acute hospitalized medical patients, Andexxa is our second FDA-approved product with the potential to save lives and have a major impact on global public health. We remain committed to our scientific leadership in the fields of thrombosis and hematologic cancers."

The approval of Andexxa is supported by data from two Phase 3 ANNEXA studies (ANNEXA-R and ANNEXA-A) published in The New England Journal of Medicine, which evaluated the safety and efficacy of Andexxa in reversing the anticoagulant activity of the Factor Xa inhibitors rivaroxaban and apixaban in healthy volunteers (Figure 1 and Figure 2, respectively). As described in the label, results demonstrated that Andexxa rapidly and significantly reversed anti-Factor Xa activity (the anticoagulant mechanism of these medicines). The median decrease in anti-Factor Xa activity from baseline was 97 percent for rivaroxaban and 92 percent for apixaban.

Interim data from the ongoing ANNEXA-4 single-arm, open-label study in patients with major bleeding also were assessed by the FDA as part of its review and approval. Data from 185 evaluable patients showed that Andexxa rapidly and significantly reversed anti-Factor Xa activity when administered as a bolus and sustained this reversal when followed by a 120-minute infusion. The median decrease from baseline was 90 percent for rivaroxaban and 93 percent for apixaban.

For additional Important Safety Information and Andexxa’s full Prescribing Information, please visit View Source

The post-marketing requirement is a clinical trial that randomizes patients to receive either Andexxa or usual care (the type of care the enrolling institution would provide in the absence of Andexxa). This study is scheduled to be initiated in 2019 and be reported in 2023.

"The expansion of available reversal agents for people prescribed newer oral anticoagulant therapies is crucial," said Randy Fenninger, chief executive officer of the National Blood Clot Alliance, a patient-led, voluntary health advocacy organization. "The availability now of a reversal agent specific to rivaroxaban and apixaban expands choice and enables patients and providers to consider these treatment options with greater confidence."

Consistent with the Company’s prior plan, Portola expects to launch Andexxa under an Early Supply Program with Generation 1 product in early June. Broader commercial launch is anticipated in early 2019 upon FDA approval of its Generation 2 manufacturing process.

The Marketing Authorization Application (MAA) for andexanet alfa is also under review by the European Medicines Agency. The Committee for Medicinal Products for Human Use (CHMP) communicated a positive trend vote on the MAA in February 2018. A formal opinion from the CHMP is expected by the end of 2018, and the European Commission is expected to issue a decision in early 2019.

Conference Call Details
The live conference call, scheduled for Friday, May 4, 2018 at 8:30 a.m. ET, can be accessed by phone by calling (844) 452-6828 from the U.S. and Canada, or 1 (765) 507-2588 internationally, and using the passcode 1357748. The webcast can be accessed live on the Investor Relations section of the Company’s website at View Source It will be archived for 30 days following the call.

About Andexxa
Andexxa is a recombinant protein specifically designed to bind to Factor Xa inhibitors and rapidly reverse their anticoagulant effect. Andexxa is a modified form of the human Factor Xa molecule, an enzyme that helps blood clot. Andexxa works by acting as a decoy for oral and injectable Factor Xa inhibitors, which target and bind to Factor Xa, which allows them to exert their anticoagulant effect. When Andexxa is given to a patient with Factor Xa inhibitor-related bleeding, it binds to the Factor Xa inhibitor and prevents it from inhibiting the activity of Factor Xa and reverses the anticoagulant effects of the inhibitor.

IMPORTANT INFORMATION FOR ANDEXXA [coagulation factor Xa (recombinant), inactivated-zhzo]

BOXED WARNING: THROMBOEMBOLIC RISKS, ISCHEMIC RISKS, CARDIAC ARREST AND SUDDEN DEATHS

See full prescribing information for complete boxed warning

Treatment with Andexxa has been associated with serious and life‑threatening adverse events, including:

Arterial and venous thromboembolic events
Ischemic events, including myocardial infarction and ischemic stroke
Cardiac arrest
Sudden deaths
Monitor for thromboembolic events and initiate anticoagulation when medically appropriate. Monitor for symptoms and signs that precede cardiac arrest and provide treatment as needed.

Indication
Andexxa [coagulation factor Xa (recombinant), inactivated-zhzo] is indicated for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

This indication is approved under accelerated approval based on the change from baseline in anti-Factor Xa (FXa) activity in healthy volunteers. An improvement in hemostasis has not been established. Continued approval for this indication may be contingent upon the results of studies to demonstrate an improvement in hemostasis in patients.

Andexxa has not been shown to be effective for, and is not indicated for, the treatment of bleeding related to any FXa inhibitors other than apixaban and rivaroxaban.

SELECT IMPORTANT SAFETY INFORMATION

Thromboembolic Risk

Arterial and venous thromboembolic events, ischemic events, sudden deaths, or events where a thrombotic event could not be ruled out were observed within 30 days post- Andexxa administration in 33 of the 185 patients (17.8%) evaluable for safety in the ongoing ANNEXA-4 study. The median time to these events was six days. Of the 86 patients who were re-anticoagulated prior to a thrombotic event, 11 (12.7%) patients experienced a thromboembolic event, ischemic event, cardiac event or death.

Monitor patients treated with Andexxa for signs and symptoms of arterial and venous thromboembolic events, ischemic events, and cardiac arrest. To reduce thromboembolic risk, resume anticoagulant therapy as soon as medically appropriate following treatment with Andexxa.

No thromboembolic events were observed in 223 healthy volunteers who received Factor Xa inhibitors and were treated with Andexxa.

The safety of Andexxa has not been evaluated in patients who experienced thromboembolic events or disseminated intravascular coagulation within two weeks prior to the life-threatening bleeding event requiring treatment with Andexxa. Safety of Andexxa also has not been evaluated in patients who received prothrombin complex concentrates, recombinant Factor VIIa, or whole blood products within seven days prior to the bleeding event.

Re-elevation or Incomplete Reversal of Anti-FXa Activity
The time course of anti-FXa activity following Andexxa administration was consistent among the healthy volunteer studies and the ANNEXA-4 study in bleeding patients. Compared to baseline, there was a rapid and substantial decrease in anti-FXa activity corresponding to the Andexxa bolus. This decrease was sustained through the end of the Andexxa continuous infusion. Following the infusion, there was an increase in anti-FXa activity, which peaked four hours after infusion in ANNEXA-4 subjects. After this peak, the anti-FXa activity decreased at a rate similar to the clearance of the FXa inhibitors.

Thirty-eight patients who were anticoagulated with apixaban had baseline levels of anti-FXa activity > 150 ng/mL. Nineteen of these 38 (50%) patients experienced a > 93% decrease from baseline anti-FXa activity after administration of Andexxa. Eleven patients who were anticoagulated with rivaroxaban had baseline anti-FXa activity levels > 300 ng/mL. Five of the 11 patients experienced a > 90% decrease from baseline anti-FXa activity after administration of Andexxa.

Adverse Reactions
The most common adverse reactions (≥ 5%) in patients receiving Andexxa were urinary tract infections and pneumonia.

The most common adverse reactions (≥ 3%) in healthy volunteers treated with Andexxa were infusion-related reactions.

Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity. Low titers of anti-Andexxa antibodies were observed in 26/145 healthy subjects (17%); 6% (9/145) were first observed at Day 30 with 20 subjects (14%) still having titers at the last time point (days 44 to 48). To date, the pattern of antibody response in patients in the ANNEXA-4 study has been similar to that observed in healthy volunteers with 6% of the patients having antibodies against Andexxa (6/98 patients). None of these anti-Andexxa antibodies were neutralizing. No antibodies cross-reacting with FX or FXa were detected in healthy subjects (0/145) or in bleeding patients to date (0/98).

Pieris Pharmaceuticals to Present at 43rd Annual Deutsche Bank Health Care Conference

On May 3, 2018 Pieris Pharmaceuticals, Inc. (NASDAQ:PIRS), a biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform for cancer, respiratory and other diseases, reported that Louis Matis, Senior Vice President and Chief Development Officer of Pieris Pharmaceuticals, Inc., will present at the 43rd Annual Deutsche Bank Healthcare Conference on Tuesday, May 8, 2018 at 8:00AM EDT at the Intercontinental Boston Hotel in Boston, Massachusetts. A webcast of the company’s presentation will be available at this link (Press release, Pieris Pharmaceuticals, MAY 3, 2018, View Source [SID1234526085]).

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Onconova Therapeutics to Present at the Disruptive Growth and Healthcare Conference on May 8th, 2018

On May 3, 2018 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, with a primary focus on myelodysplastic syndromes (MDS), reported that the Company will present and meet investors at the 2018 Disruptive Growth and Healthcare Conference in New York City (Press release, Onconova, MAY 3, 2018, View Source [SID1234526084]). Dr. Ramesh Kumar, President & CEO, will present at the event.

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Details of the Presentation:

2018 Disruptive Growth and Healthcare Conference

Reed Smith
599 Lexington Avenue, 22nd Floor
New York, NY 10022

Presentation time: 5:05-5:25 PM EDT (breakout 5:30-05:50 PM)

Presentation room: A/B

The Company is available for investor and partnering meetings

NewLink Genetics Reports First Quarter 2018 Financial Results

On May 3, 2018 NewLink Genetics Corporation (NASDAQ:NLNK) reported consolidated financial results for the first quarter 2018 and reviewed recent highlights and upcoming milestones (Press release, NewLink Genetics, MAY 3, 2018, View Source [SID1234526083]).

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"NewLink Genetics continues to produce encouraging data supporting the differentiated mechanism of action of indoximod, its IDO pathway inhibitor, and the potential for indoximod in multiple therapeutic combinations to improve patient outcomes across a broad range of cancer indications," said Charles J. Link, Jr, MD, Chairman and Chief Executive Officer.
Highlights

Abstracts accepted for presentation at the ASCO (Free ASCO Whitepaper) Annual Meeting, June 2018

Abstract 4015 – Phase 2 trial of the IDO pathway inhibitor indoximod plus gemcitabine / nab-paclitaxel for the treatment of patients with metastatic pancreas cancer – to be presented during the discussion session, "Gastrointestinal (Noncolorectal) Cancer," Sunday, June 3, 2018, 4:45 PM – 6:00 PM CT

Abstract 9512 – Phase 2 trial of the IDO pathway inhibitor indoximod plus checkpoint inhibition for the treatment of patients with advanced melanoma – to be presented during the discussion session, "Melanoma/Skin Cancers," Monday, June 4, 2018, 4:45 PM – 6:00 PM CT

Abstracts presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, April 2018

Abstract 3753 – Indoximod modulates AhR-driven transcription of genes that control immune function

Abstract 10973 – Front-line therapy of DIPG using the IDO pathway inhibitor indoximod in combination with radiation and chemotherapy

Abstract, Radio-immunotherapy using the IDO pathway inhibitor indoximod for children with newly-diagnosed DIPG, to be presented at the 18th International Symposium on Pediatric Neuro-Oncology (ISPNO), Poster Session 1, Sunday, July 1, 2018, 5:00 PM – 6:30 PM MT

Data from Phase 1b trial of indoximod plus standard-of-care chemotherapy for patients with acute myeloid leukemia (AML) intended to be presented in the second half of 2018

Finalized the novel formulation of indoximod

Update on Clinical Programs and Financial Guidance
NewLink Genetics previously reported that it was undertaking a review of its clinical programs and determined it will not initiate its Phase 3 study of indoximod in combination with PD-1 inhibitors for patients with advanced melanoma. In addition, we have deprioritized pancreatic cancer and have mutually agreed with AstraZeneca not to proceed with the Phase 2 trial.
Clinical opportunities under consideration include high quality randomized studies of indoximod in one or more target disease states for which we have developed promising single-arm data over the last few years. Indoximod has demonstrated encouraging clinical data in a number of cancer indications including AML in combination with chemotherapy, DIPG in combination with radiation and chemotherapy, and melanoma in combination with checkpoint

Exhibit 99.1

blockade. When we complete the review of our clinical programs, we expect to have substantially reduced the rate at which the Company will be using cash. We intend to update our financial guidance when we report results for the second quarter.
Financial Results
Cash Position: NewLink Genetics ended the quarter on March 31, 2018, with cash and cash equivalents totaling $143.9 million compared to $158.7 million for the year ending December 31, 2017.
R&D Expenses: Research and development expenses for the three months ended March 31, 2018 were $20.3 million, an increase of $4.6 million from $15.7 million for the same period in 2017. The increase was due primarily to an increase of $8.4 million in contract research and manufacturing spend, an increase of $670,000 in clinical trial and legal and consulting expense, offset by a $2.1 million decrease in supplies, a $1.2 million decrease in personnel-related and stock compensation expense, and a $1.2 million decrease in licensing expenses.
G&A Expenses: General and administrative expenses for the three months ended March 31, 2018 were $8.3 million, an increase of $58,000 from $8.2 million for the same period in 2017. The increase was due to an increase of $733,000 of legal and consulting and other expense, offset by a decline of $675,000 in personnel-related and stock compensation.
Net Loss: The net loss for the three months ended March 31, 2018 was $18.3 million compared to net loss of $20.9 million for the same period in 2017. The basic and diluted weighted average common shares outstanding for the three months ended March 31, 2018 were 37,155,082, resulting in a basic and diluted loss per share of $0.49. For the three months ended March 31, 2017, the basic and diluted weighted average common shares outstanding were 29,213,488, resulting in basic and diluted loss per share of $0.72.
NewLink Genetics ended Q1 2018 with 37,165,098 shares outstanding.
Conference Call and Webcast Details
The Company has scheduled a conference call and webcast for 4:30 p.m. ET today to discuss the financial results and to review its clinical activities. NewLink Genetics’ senior management team will host the call, which will be open to all listeners. There will also be a question and answer session following the prepared remarks.
Access to the live call is available by dialing (855) 469-0612 (U.S.) or (484) 756-4268 (international) five minutes prior to the start of the call. The conference call will be webcast live and a link can be accessed through the NewLink Genetics website at View Source To ensure a timely connection, it is recommended that users register at least 15 minutes prior to the scheduled webcast. A replay of the call will be available for two weeks from the date of the call and can be accessed by dialing (855) 859-2056 (U.S.) or (404) 537-3406 (international) and using the passcode 6768809.
About Indoximod
Indoximod is an investigational, orally available small molecule targeting the IDO pathway. The IDO pathway is a key immuno-oncology target involved in regulating the tumor microenvironment and immune escape. Indoximod is being evaluated in combination with treatment regimens including chemotherapy, radiation, checkpoint blockade and cancer vaccines across multiple indications such as AML, DIPG and melanoma.

NANOBIOTIX PARTNERS WITH WEILL CORNELL MEDICINE ON PRE-CLINICAL STUDIES
TO EVALUATE THE IMPACT OF NBTXR3 ON cGAS-STING PATHWAY IN MAMMARY CANCERS

On May 3, 2018 NANOBIOTIX (Euronext: NANO – ISIN: FR0011341205), a late clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, reported that it is launching a research collaboration with Weill Cornell Medicine to begin nonclinical studies of NBTXR3’s mechanism of action (Press release, Nanobiotix, MAY 3, 2018 View Source [SID1234526080]). NBTXR3 is a first-in-class product designed to destroy, when activated by radiotherapy, tumors and metastasis through physical cell death and to induce immunogenic cell death leading to specific activation of the immune system.

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The research collaboration between Weill Cornell Medicine, based in New York City, and Nanobiotix will be conducted
over the course of one year, with the goal of continuing the exploration of the role of NBTXR3 in Immuno-Oncology.
The main objective of this collaboration is to study the impact of NBTXR3 activated by radiotherapy on the cGAS-STING
pathway using different in vitro and in vivo murine models (mammary). Along with immunogenic cell death, the cGASSTING
pathway has emerged as the key component of the anti-tumor immune response. Data generated from this
collaboration could support current evidence indicating that NBTXR3 activated by radiotherapy can increase the antitumor
immune response, compared with radiotherapy alone, and transform an irradiated tumor into an efficient in
situ vaccine.
Dr. Sandra Demaria, M.D., Professor of Radiation Oncology and Chief of the Division of Experimental Radiotherapy in
the Department of Radiation Oncology at Weill Cornell Medicine, and Principal Investigator for the study, said: "We
have learned that radiotherapy has the potential to convert a tumor into an in-situ vaccine, and enhance systemic
tumor responses to immunotherapy. But there is room for improvement: NBTXR3 nanoparticles enhance the proimmunogenic
effects of radiotherapy, and we want to understand how they work. This knowledge will further the
development of this innovative approach for the treatment of cancer patients who are resistant to immune checkpoint
inhibitors."
The Company received the FDA’s approval to launch a clinical study of NBTXR3 activated by radiotherapy in
combination with anti-PD1 antibody in lung, and head and neck cancer patients (head and neck squamous cell
carcinoma and nonsmall cell lung cancer). This trial that shall start in Q2 2018, aims to expand the potential of NBTXR3,
including using it to treat recurrent or metastatic disease.
NBTXR3 positioning in IO
Many IO combination strategies focus on ‘priming’ the tumor, which is now becoming a prerequisite of turning a "cold"
tumor into a "hot" tumor.
Compared to other modalities that could be used for priming the tumor, NBTXR3 could have a number of advantages:
the physical and universal mode of action that could be used widely across oncology, a one-time local injection and
good fit within existing medical practice already used as a basis for cancer treatment, as well as a very good chronic
safety profile and well-established manufacturing process.
Published preclinical and clinical data indicate that NBTXR3 could play a key role in oncology and could become a
backbone in immuno-oncology.
Nanobiotix’s immuno-oncology combination program opens the door to new developments, potential new
indications, and important value creation opportunities.
-ends-
2
About NBTXR3
NBTXR3 is a first-in-class product designed to destroy, when activated by radiotherapy, tumors and metastasis through physical
cell death and to immunogenic cell death leading to specific activation of the immune system.
NBTXR3 has a high degree of biocompatibility, requires one single administration before the whole radiotherapy treatment and
has the ability to fit into current worldwide standards of radiation care.
NBTXR3 is being evaluated in head and neck cancer (locally advanced squamous cell carcinoma of the oral cavity or oropharynx),
and the trial targets frail and elderly patients who have advanced cancer with very limited therapeutic options. The Phase I/II trial
has already delivered very promising results regarding the local control of the tumors and a potential metastatic control through
in situ vaccination.
Nanobiotix is running an Immuno-Oncology program with NBTXR3 that includes several studies. In the U.S., the Company received
the FDA’s approval to launch a clinical study of NBTXR3 activated by radiotherapy in combination with anti-PD1 antibodies in lung,
and head and neck cancer patients (head and neck squamous cell carcinoma and non-small cell lung cancer). This trial aims to
expand the potential of NBTXR3, including using it to treat recurrent or metastatic disease.
The first market authorization process (CE Marking) is ongoing in Europe in the soft tissue sarcoma indication.
The other ongoing studies are treating patients with liver cancers (hepatocellular carcinoma and liver metastasis), locally advanced
or unresectable rectal cancer in combination with chemotherapy, head and neck cancer in combination with concurrent
chemotherapy, and prostate adenocarcinoma.