phas-8k_20190409.htm

 

 

 

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

FORM 8-K

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): April 9, 2019

 

PhaseBio Pharmaceuticals, Inc.

(Exact name of Registrant as Specified in Its Charter)

 

 

Delaware

001-38697

03-0375697

(State or Other Jurisdiction

of Incorporation)

(Commission

File Number)

(IRS Employer

Identification No.)

 

1 Great Valley Parkway, Suite 30

Malvern, Pennsylvania

 

19355

(Address of Principal Executive Offices)

 

(Zip Code)

(610) 981-6500

(Registrant’s Telephone Number, Including Area Code)

Not Applicable

(Former Name or Former Address, if Changed Since Last Report)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instructions A.2. below):

 

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company  

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  

 

 

 


 

Item 7.01Regulation FD Disclosure.

 

On April 9, 2019, PhaseBio Pharmaceuticals, Inc. (the “Company”) made available an updated version of the Company’s corporate presentation on the Company’s website. A copy of the updated corporate presentation is furnished as Exhibit 99.1 to this Current Report on Form 8-K.

 

The information in this Item 7.01 of this Current Report on Form 8-K (including Exhibit 99.1) is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Exchange Act or otherwise subject to the liabilities of that Section, nor shall it be deemed incorporated by reference in any filing under the Securities Act or the Exchange Act, except as expressly set forth by specific reference in such a filing.

 

Item 8.01Other Events.

 

On April 9, 2019, the Company issued a press release announcing the commencement of an underwritten public offering of its common stock (the “Offering”). A copy of the press release is filed as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference. 

 

In connection with the Offering, the Company filed a registration statement on Form S-1 on April 9, 2019, which includes certain updated information concerning the Company and its business strategy, as set forth below:

 

Overview

 

We are a clinical-stage biopharmaceutical company focused on the development and commercialization of novel therapies to treat orphan diseases, with an initial focus on cardiopulmonary indications. Our lead product candidate, PB2452, is a novel reversal agent for the antiplatelet drug ticagrelor, which we are developing for the treatment of patients on ticagrelor who are experiencing a major bleeding event or those who require urgent surgery. We recently completed a Phase 1 clinical trial of PB2452 in healthy subjects and intend to initiate a Phase 2a clinical trial in healthy older subjects in the first half of 2019. The United States Food and Drug Administration, or FDA, granted breakthrough therapy designation for PB2452 in April 2019. Our second product candidate, PB1046, is a once-weekly fusion protein currently in a Phase 2b clinical trial for the treatment of pulmonary arterial hypertension, or PAH. PB1046 utilizes our proprietary half-life extending elastin-like polypeptide, or ELP, technology, which also serves as the engine for our preclinical pipeline. We retain worldwide rights to all of our product candidates.

 

PB2452 is a novel recombinant human monoclonal antibody antigen-binding fragment, or Fab fragment, designed to reverse the antiplatelet activity of ticagrelor. Ticagrelor is an antiplatelet therapy widely prescribed to reduce the rates of death, heart attack and stroke in patients with acute coronary syndrome, or ACS, or who have previously experienced a heart attack. The American College of Cardiology, American Heart Association and European Society of Cardiology guidelines recognize ticagrelor as the preferred antiplatelet therapy for ACS. In 2018, ticagrelor, currently marketed by AstraZeneca plc, or AstraZeneca, under the brand names Brilinta and Brilique, had worldwide sales of $1.3 billion, an increase of 22% over 2017 sales. In the fourth quarter of 2018, ticagrelor had worldwide sales of $376 million, an increase of 26% over sales in the fourth quarter of 2017. Ticagrelor binds and inhibits the platelet P2Y12 receptor to prevent platelets from forming obstructive blood clots, which could block blood flow to critical organs in these patients, causing heart attacks or strokes. Due to ticagrelor’s antiplatelet activity, patients on ticagrelor have an elevated risk of spontaneous bleeding. In addition, patients on ticagrelor who need urgent surgery cannot wait the recommended five days for ticagrelor’s effect to dissipate and are at increased risk of major bleeding during and after surgery. There are currently no known reversal agents approved or in clinical development for ticagrelor or any of the other antiplatelet drugs. In our Phase 1 clinical trial, PB2452 achieved immediate and sustained reversal of ticagrelor’s antiplatelet activity, with potential customizable duration of reversal based on the dosing regimen, which we believe has the potential to bring life-saving therapeutic benefit to these patients by increasing the safety of ticagrelor. We believe the availability of a reversal agent could expand ticagrelor’s use by mitigating concerns regarding bleeding risk and uniquely position ticagrelor as the only oral antiplatelet drug with a reversal agent.

 

We recently completed a Phase 1 dose escalation clinical trial of PB2452 in healthy subjects ages 18 to 50 who had been pre-dosed with ticagrelor. In this trial, we observed immediate and complete reversal of ticagrelor’s antiplatelet activity within five minutes following initiation of infusion, and sustained reversal for over 20 hours in dosing cohorts in which we administered PB2452 over an extended infusion period. Based on our observations in our Phase 1 trial, duration of reversal may be controlled by duration of the infusion, which may allow for customization based on patient needs. There were no PB2452-related adverse events, or AEs, or serious adverse events, or SAEs, in any of the dose cohorts. We believe that the results of the Phase 1 trial support the continued development of PB2452 to treat ticagrelor patients who are experiencing a major bleeding event or those who require urgent surgery.

 

We intend to initiate a Phase 2a clinical trial of PB2452 in generally healthy older and elderly subjects in the first half of 2019 in order to evaluate safety and efficacy of the potentially therapeutic doses and dosing regimens from the Phase 1 trial in this population. Older adults exhibit more variability in drug response to ticagrelor and higher levels of baseline platelet reactivity

 


 

compared to younger subjects, and they resemble the patient population most likely to be treated with ticagrelor and potentially benefit from PB2452, if approved. We intend to design the Phase 2a trial to identify the most appropriate dose and dosing regimen of PB2452 for our planned Phase 2b and Phase 3 clinical trials.

 

The FDA granted breakthrough therapy designation for PB2452 in April 2019. In mid-2019, we intend to request a meeting with the FDA to review the clinical profile of and confirm the regulatory pathway for PB2452. Subject to discussions with the FDA, we intend to initiate a multi-center Phase 2b clinical trial of PB2452 in healthy older adults in the second half of 2019 and an international, multi-center Phase 3 clinical trial in patients on ticagrelor who are experiencing a major bleeding event or require urgent surgery in 2020. The FDA’s accelerated approval regulations allow drugs that are being developed to treat an unmet medical need for serious conditions to be approved substantially based on evidence of an effect on a surrogate biomarker endpoint that is considered reasonably likely to predict clinical benefit, rather than a clinical endpoint such as survival or irreversible morbidity. If considered appropriate by the FDA, we intend to pursue accelerated approval, which would allow us to submit a biologics license application, or BLA, prior to completion of the Phase 3 clinical trial based on biomarker data from an initial subset of the Phase 3 patients. If we were to receive accelerated approval, the completion of the Phase 3 trial would be a post-marketing commitment.

 

PB1046 is being developed as a once-weekly, novel treatment for PAH, a progressive, life-threatening, orphan disease caused by vasoconstriction and structural deterioration of the pulmonary arteries, which can lead to heart failure and, eventually, death. PB1046 is a subcutaneously-injected, sustained release analogue of the native human peptide vasoactive intestinal peptide, or VIP. VIP is a neurohormone that relaxes the muscles surrounding blood vessels, causing them to dilate, which results in improved blood flow. In contrast to the currently approved therapies for PAH, which only target vasodilation, we believe that VIP also suppresses the adverse remodeling of blood vessels and increases cardiac contractility and relaxation. We believe that PB1046 has the potential to be disease-modifying and complementary to current standard of care therapies for PAH.

 

We have completed two clinical trials of subcutaneously-injected PB1046 in subjects with cardiovascular diseases. In these trials, PB1046 was observed to be well tolerated, with no drug-related SAEs. In both trials, we observed that patients who received PB1046 experienced statistically significant reductions in blood pressure that were sustained for at least one week, with no reported episodes of symptomatic hypotension. We have also completed enrollment of an exploratory Phase 1b/2a clinical trial to evaluate the effects of PB1046 on pulmonary arterial pressure in PAH patients with a CardioMEMS device, an implanted hemodynamic monitor that continuously reports pulmonary arterial pressure and cardiac function. In preliminary results from this trial, we have observed reductions in pulmonary arterial pressure and increases in cardiac output, which we believe are consistent with potential beneficial effects of PB1046. As of the date of this prospectus, we have observed one drug-related SAE of vasodilation in one patient in the extension portion of the open-label pilot study of this trial. We have begun dosing patients in a randomized, double-blinded, parallel group Phase 2b clinical trial in approximately 60 PAH patients to assess the safety, tolerability and efficacy of PB1046. This clinical trial will evaluate the effects of PB1046 on pulmonary arterial pressure and exercise tolerance, including the distance the patient can walk in six minutes, which is an important clinical endpoint that the FDA has previously used as the basis for approval of other PAH drugs. We expect to report results from this trial in 2020.

 

PB1046 and our preclinical product candidates are based on our proprietary ELP technology. Our ELP technology extends the circulating half-life of proteins and peptides and also provides a sustained-release mechanism, resulting in exposure of active molecules for periods of a week or longer from a single subcutaneous injection. We believe that our ELP technology enhances solubility, stability and bioavailability, provides extended drug exposure and creates product candidates that are straightforward to manufacture and administer. Our strategy is to apply our ELP technology to proteins and peptides with well-characterized therapeutic activities but suboptimal half-lives to improve their pharmacokinetics, enable their use as pharmaceutical products and allow for more convenient dosing regimens. To date, we have not observed any drug-related SAEs in any of the over 500 subjects in clinical trials of our ELP product candidates.

 

We have an experienced management team that includes individuals with experience in translational research, orphan and cardiopulmonary drug discovery, development and commercialization. We are led by our Chief Executive Officer, Jonathan P. Mow, who brings more than 25 years of experience in biotechnology management, including previous executive experience at Amylin Pharmaceuticals, Corus Pharma, PathoGenesis and Bristol-Myers Squibb.


 


 

 

Pipeline

 

Our clinical-stage and pre-clinical pipeline is set forth below:

 

 

Recent Developments

 

Breakthrough Therapy Designation

 

In April 2019, the FDA granted breakthrough therapy designation for PB2452 for the reversal of ticagrelor’s antiplatelet activity.  The breakthrough therapy designation was supported by our Phase 1 trial results, in which we observed immediate and complete reversal of ticagrelor’s antiplatelet activity within five minutes following initiation of infusion, and sustained reversal for over 20 hours in dosing cohorts in which we administered PB2452 over an extended infusion period.

 

ImmunoForge License Agreement

 

In April 2019, we entered into a license agreement with ImmunoForge, Co. Ltd. for the exclusive, worldwide license of PB1023 for the treatment of certain diseases, including conditions related to sarcopenia. PB1023 is a long-acting, recombinant glucagon-like peptide-1 analogue. We previously ceased development of PB1023 for the treatment of hyperglycemia associated with type 2 diabetes.  We retained the right to develop PB1023 for the treatment of diabetes, obesity and non-alcoholic steatohepatitis.  Pursuant to the agreement, we will receive a nominal upfront payment and are eligible to receive development milestone payments and mid-single digit royalty payments on net sales of licensed products, a percentage of which Duke University is entitled to receive pursuant to the terms of our existing license agreement.

 

Forward-Looking Statements

 

This Current Report on Form 8-K contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and other federal securities laws. Any statements contained herein that do not describe historical facts, including, but not limited to, statements regarding the anticipated use of proceeds of the Offering, the timing of completion of the Offering, our clinical trials and our research, development and regulatory plans for PB2452, PB1046 and our ELP research programs, the development of PB1023 and our receipt of milestone and royalty payments from ImmunoForge are forward-looking statements that involve risks and uncertainties that could cause actual results to differ materially from those discussed in such forward-looking statements. Such risks and uncertainties include, among others, the risks identified in the Company’s filings with the Securities and Exchange Commission (the “SEC”), including those described under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2018, as well as those discussed in the prospectus related to the Offering and subsequent filings with the SEC. Any of these risks and uncertainties could materially and adversely affect the Company’s results of operations, which would, in turn, have a significant and adverse impact on the Company’s stock price. The Company cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. The Company undertakes no obligation to update publicly any forward-looking statements to reflect new information, events or circumstances after the date they were made or to reflect the occurrence of unanticipated events.


 


 

Item 9.01 Financial Statements and Exhibits.

 

(d)Exhibits

 

 

 

 

Exhibit No.

 

Description

 

 

99.1

 

Corporate Presentation, dated April 2019.

 

 

99.2

 

Press Release, dated April 9, 2019, titled “PhaseBio Announces Proposed Public Offering of Common Stock.”

 

 

 

 

 

 


 


 

 

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

 

 

 

PhaseBio Pharmaceuticals, Inc.

 

 

 

 

Dated: April 9, 2019

 

By:

/s/ John Sharp

 

 

 

John Sharp

 

 

 

Chief Financial Officer

 

 

phas-ex991_11.pptx.htm

Slide 1

Corporate Overview April 2019 Exhibit 99.1

Slide 2

Legal Disclaimer This presentation includes forward-looking statements. All statements contained in this presentation other than statements of historical facts, including statements regarding future results of operations and financial position of PhaseBio Pharmaceuticals, Inc. (“we,” “us” or “our”) our business strategy and plans, the preclinical and clinical development of our product candidates and our objectives for future operations, are forward-looking statements. The words “anticipate,” believe,” “continue,” “estimate,” “expect,” “intend,” “may,” “will” and similar expressions are intended to identify forward-looking statements. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our financial condition, results of operations, business strategy, clinical development, short-term and long-term business operations and objectives and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions. Risks regarding our business are described in detail in our Securities and Exchange Commission filings, including in our Annual Report on Form 10-K for the year ended December 31, 2018. Moreover, we operate in a very competitive and rapidly changing environment. New risks emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. In light of these risks, uncertainties and assumptions, the future events and trends discussed in this presentation may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance, achievements or events and circumstances reflected in the forward-looking statements will occur. We are under no duty to update any of these forward-looking statements after the date of this presentation to conform these statements to actual results or revised expectations, except as required by law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this presentation. Moreover, except as required by law, neither we nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements contained in this presentation.

Slide 3

Company Overview Therapeutic Focus Clinical-stage biopharma company focused on the development and commercialization of novel therapies to treat orphan diseases, with an initial focus on cardiopulmonary indications Product Candidates PB2452 – Novel agent for immediate and sustained reversal of ticagrelor, the preferred antiplatelet therapy of the American College of Cardiology, the American Heart Association and European Society of Cardiology PB1046 – Once-weekly novel treatment for pulmonary arterial hypertension (PAH), based on elastin-like polypeptide (ELP) technology, that is vasodilatory, potentially disease-modifying and complementary to current standard-of-care therapies Platform Technology ELP Technology Extends circulating half-life of proteins and peptides and provides a sustained-release mechanism Enhances solubility, stability and bioavailability, provides extended drug exposure Creates product candidates that are straightforward to manufacture and administer Milestones & Catalysts 2019 PB2452 March 17, 2019 Late-breaking oral presentation of full Phase 1 results at the American College of Cardiology’s Annual Scientific Session/ Simultaneous publication in New England Journal of Medicine PB2452 April 8, 2019 Granted Breakthrough Therapy designation by FDA PB2452 1H 2019 Initiate Phase 2a trial in healthy older adults PB2452 1H 2019 Report results from Phase 2a trial in healthy older adults PB2452 2H 2019 Initiate large Phase 2b trial in healthy older adults to support BLA safety database 2020 PB1046 1H 2020 Phase 2b data PB2452 2020 Initiate Phase 3 study based on plan to pursue accelerated approval pathway

Slide 4

Program Indication/Therapeutic Area Pre-Clinical Phase 1 Phase 2 Phase 3 WW Commercial Rights Milestones PB2452 Reversal of Ticagrelor Antiplatelet Activity 1H 2019: Initiate Phase 2a Report Phase 2a results 2H 2019: Initiate Phase 2b 2020: Initiate Phase 3 based on plan to pursue accelerated regulatory pathway PB1046 Pulmonary Arterial Hypertension (PAH) 2020: Phase 2b results GLP2-ELP Short Bowel Syndrome CNP-ELP Achondroplasia Early Programs A Clinical Stage, Orphan Disease-Focused Biopharmaceutical Company Phase 2 ongoing Breakthrough Therapy Designation granted in April 2019 Late research PROPRIETARY LONG ACTING INJECTABLE RECOMBINANT BIOPOLYMERS (Elastin-like Polypeptides – ELPs) ELP TECHNOLOGY PLATFORM DRIVES INTERNAL DISCOVERY IND-enabling activities Phase 2 ongoing

Slide 5

Corporate

Slide 6

Recent Corporate Highlights PB2452 granted Breakthrough Therapy designation by FDA in April 2019 Breakthrough Therapy designation is designed to expedite the development and review of promising new drugs Reported PB2452 Phase 1 results Presented as a late breaking oral presentation at the American College of Cardiology’s Annual Scientific Session on March 17, 2019 Simultaneously published in the New England Journal of Medicine Secured up to $15 million term loan facility from Silicon Valley Bank Funds to repay existing $7.5M term loan in full and support advancement of PB2452: March 2019 Dosed first patient in PB1046 Phase 2b trial for the treatment of pulmonary arterial hypertension (PAH) Dosed first patient in a multi-center, randomized, double-blind, parallel-group Phase 2b trial: November 2018 Cash balance at year-end 2018: $61.0M Well capitalized to execute development plan

Slide 7

Full-Year 2018 Financial Highlights Operating expense: $20.3M R&D: $15.5M SG&A: $4.9M Loss from Operations: ($19.6M) Net Loss of ($23.8M) or ($4.49) per share 5.3M shares used for computing FY 2018 net loss per share Cash and cash equivalents as of 12/31/2018: $61.0M Shares outstanding as of 03/15/2019: 24,498,425 All values in USD millions except share counts and net loss per share Numbers may not sum to totals due to rounding

Slide 8

Experienced Management Team JONATHAN MOW Chief Executive Officer Amylin Pharmaceuticals, Corus Pharma, PathoGenesis, BMS JOHN SHARP Chief Financial Officer Ligand Pharmaceuticals, HUYA Bioscience, Sequenom, Diversa JOHN LEE, MD, PhD, FACC Chief Medical Officer Merck, BMS, Quintiles SUSAN ARNOLD, PhD VP of Preclinical & CMC Targeted Genetics, Viromed Biosafety Labs, BioRexis, NuPathe JIM BALLANCE, PhD VP Research & Scientific Affairs Delta Biotechnology, Aventis Behring, BioRexis MICHAEL YORK VP Corp Development & Commercial Strategy Orexigen, Amylin Pharmaceuticals, Santarus, Amgen, AstraZeneca GLEN BURKHARDT VP Human Resources Hologic, Onyx Pharmaceuticals, Eli Lilly

Slide 9

PB2452 – Reversal Agent for Ticagrelor

Slide 10

PB2452 - Novel reversal agent for Brilinta (ticagrelor) Human monoclonal antibody fragment (Fab), delivered intravenously in the hospital Phase 1 Proof of Concept Study completed Selected for late-breaking oral presentation American College of Cardiology’s Annual Scientific Session (March 17, 2019) Simultaneously published in the New England Journal of Medicine Immediate and sustained reversal of ticagrelor anti-platelet effects P2Y12 receptor antagonist with demonstrated superior efficacy to clopidogrel Reversal agent availability would differentiate ticagrelor on safety vs. other oral antiplatelet agents Growth in ticagrelor share of P2Y12 market would increase need for reversal agent Significant unmet need for antiplatelet agent reversal All oral antiplatelet agents have the potential to cause major bleeding, which can be severe or even fatal PB2452 immediately and sustainably reverses the antiplatelet effects of ticagrelor Currently oral P2Y12 agents, including ticagrelor, require a ≥5 day washout prior to surgery1,2 Urgent surgery cannot wait 5 days High thrombotic risk during washout In the Phase 1 study, PB2452 immediately and sustainably reversed ticagrelor inhibition of platelet activation Enables immediate surgery Active Major Bleeding Urgent Surgery or Intervention Plavix/clopidogrel Prescribing Information: https://packageinserts.bms.com/pi/pi_plavix.pdf, https://www.ema.europa.eu/en/documents/product-information/plavix-epar-product-information_en.pdf Brilinta/Brilique/ticagrelor Prescribing Information: https://www.azpicentral.com/brilinta/brilinta.pdf#page=1, https://www.ema.europa.eu/en/documents/product-information/brilique-epar-product-information_en.pdf

Slide 11

PB2452: Well-Characterized Mechanism of Reversal of Ticagrelor ADP ADP Platelet ADP binds to P2Y12 receptor causing platelet aggregation Ticagrelor binds to P2Y12, inhibiting ADP-induced platelet aggregation This is a reversible process with ticagrelor cycling on/off the P2Y12 receptors PB2452:ticagrelor is eliminated from the bloodstream PB2452:ticagrelor binding is preferential to ticagrelor:P2Y12 binding As free ticagrelor is eliminated, ADP can again activate the P2Y12 receptor, restoring platelet activity PB2452 binds to free ticagrelor with very high affinity PB2452 4. 5. 6. 1. 2. 3. ADP ADP Platelet ADP Ticagrelor P2Y12 Receptor ADP

Slide 12

PB2452 Granted Breakthrough Therapy Designation In April 2019, PB2452 was granted Breakthrough Therapy designation by FDA Designation supported by Phase 1 trial results, which were recently published in the New England Journal of Medicine1 Breakthrough Designation may be granted by FDA when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies Breakthrough Therapy designation offers companies the following benefits designed to expedite the review process2: Intensive guidance on an efficient drug development program, beginning as early as Phase 1 Organizational commitment involving senior managers All Fast Track designation features including more frequent meetings with FDA and more frequent written communication from FDA Companies may also be eligible for Accelerated Approval and Priority Review, if relevant criteria are met Bhatt, D. L. et al. Antibody-based ticagrelor reversal agent in healthy volunteers. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa1901778 (2019) The U.S. Food and Drug Administration. “Expedited Programs for Serious Conditions – Drugs and Biologics.” Available at: https://www.fda.gov/downloads/Drugs/Guidances/UCM358301.pdf. Accessed April 2019

Slide 13

PB2452 Phase 1 Proof-of-Concept Study in Healthy Subjects Selected as late-breaking oral presentation during featured clinical research session at the American College of Cardiology’s Annual Scientific Session – March 17, 20191 Simultaneously published in the New England Journal of Medicine2 https://www.acc.org/latest-in-cardiology/clinical-trials/2019/03/15/21/37/ticagrelor-reversal-agent Bhatt DL, Pollack CV, Weitz JI, et al. Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers. N Engl J Med 2019;Mar 17:[Epub ahead of print].

Slide 14

PB2452 Phase 1 Proof-of-Concept Study in Healthy Subjects Randomized, double-blind, placebo-controlled, single ascending dose (SAD), sequential group study (n=64) 3:1 randomization, PB2452-Placebo Higher-dose cohorts pre-treated with ticagrelor After 48 hours of ticagrelor, platelet aggregation was suppressed by ~80%, as expected based on approved package insert Platelet function evaluated using three well established and commonly used assays: LTA, VerifyNow P2Y12 and VASP Results from all three assays were highly correlated Onset of reversal occurred within 5 minutes and was sustained for over 20 hours P<0.001 across all timepoints, Bonferroni adjusted Well tolerated with no drug-related serious adverse events No evidence of rebound in platelet activity after drug cessation LTA = light transmittance aggregometry, VASP = vasodilator stimulated phosphoprotein phosphorylation immunoassay Bhatt DL, Pollack CV, Weitz JI, et al. Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers. N Engl J Med 2019;Mar 17:[Epub ahead of print].

Slide 15

PB2452 Phase 1 Trial Design Cohort Ticagrelor Pretreatment PB2452 IV regimen Volunteers Active:Placebo 1 None 0.1g 30 min 3A:1P 2 None 0.3g 30 min 3A:1P 3 None 1g 30 min 3A:1P 4 180mg PO + 90mg BID x 2 days 1g 30 min 6A:2P 5 180mg PO + 90mg BID x 2 days 3g 30 min 6A:2P 6 180mg PO + 90mg BID x 2 days 9g 30 min 6A:2P 7 180mg PO + 90mg BID x 2 days 18g (3g 5 min + 15g 7 hr 55 min) 6A:2P 8 180mg PO + 90mg BID x 2 days 18g (6g 15 min + 6g 3 hr + 6g 8hr 45 min) 6A:2P 9 180mg PO + 90mg BID x 2 days 18g (6g 15 min + 6g 4 hr + 6g 12 hr) 3A:1P 10 180mg PO + 90mg BID x 2 days 18g (6g 10 min + 6g 3 hr + 6g 13 hr) 6A:2P Cohorts 9 and 10 achieved study objectives and will be the basis for dosing in the Phase 2a study in generally healthy older volunteers Bhatt DL, Pollack CV, Weitz JI, et al. Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers. N Engl J Med 2019;Mar 17:[Epub ahead of print]. g = grams, min= minutes, A = active, P = placebo, mg=milligrams, hr=hours, PO=orally, BID= twice per day

Slide 16

Nominal Time (h) Platelet Function After Ticagrelor Reversal - LTA Normalization of platelet response to ADP was assessed by whether reversal of ticagrelor achieved a normal range of platelet function Bhatt DL, Pollack CV, Weitz JI, et al. Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers. N Engl J Med 2019;Mar 17:[Epub ahead of print]. Return to Normal Platelet Function: Post-PB2452 Dosing Inhibited Platelet Function: Post-Ticagrelor Dosing Normal Platelet Function: Pre-Ticagrelor Dosing Normal Platelet Function Inhibited Platelet Function LTA= light transmittance aggregometry; Adenosine Diphosphate (ADP) is the agonist Shown are data from cohorts 9 and 10 (pooled) Cohorts 9 and 10 achieved study objectives and will be the basis for dosing in the Phase 2a study in generally healthy older volunteers Dose-dependent response across all cohorts tested Immediate reversal within 5 minutes of start of infusion Sustained duration of reversal extended to 20+ hours Rapid resumption of ticagrelor dosing post infusion Well tolerated across all cohorts No drug-related SAEs

Slide 17

%Platelet aggregation by AA Nominal Time (h) Platelet Aggregation with AA and TRAP Mean platelet aggregation by LTA using AA (top) or TRAP (bottom) as agonist %Platelet aggregation by TRAP Nominal Time (h) Arachidonic acid (AA) Thrombin receptor activating peptide (TRAP) No platelet rebound effect observed Absence of platelet hyper-reactivity, or rebound effect with arachidonic acid and thrombin receptor activating peptide between 5 minutes and 48 hours Platelet rebound between 5 minutes and 48 hours was also ruled out by the response to low-dose ADP versus high-dose ADP* Bhatt DL, Pollack CV, Weitz JI, et al. Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers. N Engl J Med 2019;Mar 17:[Epub ahead of print]. *ADP data presented by Dr. Deepak L. Bhatt at the American College of Cardiology Annual Scientific Session (ACC 2019), New Orleans, LA, March 17, 2019. Slides available at: https://www.acc.org/~/media/Clinical/PDF-Files/Approved-PDFs/2019/03/15/ACC19_Slides/Mar17_Sun/3pmET_Ticagrelor-Reversal-Agent-acc-2019.pdf

Slide 18

Treatment-Emergent Adverse Events  Preferred Term All Placebo (N=16) n (%) All PB2452 (N=48) n (%) Total Number of TEAEs 3 27 Number of volunteers with at Least 1 TEAE 2 (12.5) 17 (35.4) Infusion site bruising 0 4 (8.3) Medical device site reaction 0 3 (6.3) Infusion site extravasation 0 2 (4.2) Vessel puncture site bruise 0 2 (4.2) Abdominal pain 0 1 (2.1) Acute respiratory failure 0 1 (2.1) Alcohol poisoning 0 1 (2.1) Blood urine present 0 1 (2.1) Conjunctivitis 0 1 (2.1) Contusion 1 (6.3) 0 Dizziness 0 1 (2.1) Eyelid irritation 1 (6.3) 0 Gastroenteritis 0 1 (2.1) Hematuria 0 1 (2.1) Infusion site reaction 0 1 (2.1) Musculoskeletal chest pain 1 (6.3) 0 Nasopharyngitis 0 1 (2.1) Oropharyngeal pain 0 1 (2.1) Pharyngitis streptococcal 0 1 (2.1) Pneumonia aspiration 0 1 (2.1) Skin abrasion 0 1 (2.1) Upper limb fracture 0 1 (2.1) Treatment-emergent adverse events were limited mostly to mild injection site issues Bhatt DL, Pollack CV, Weitz JI, et al. Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers. N Engl J Med 2019;Mar 17:[Epub ahead of print].

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PB2452 Clinical Development Plan Based on FDA Accelerated Approval Pathway Regulatory Strategy Based on Pre-IND Discussion of Accelerated Approval Phase 2a trial to confirm dosing in an older, healthy-for-age population Large Phase 2b trial will develop BLA safety database Phase 3 non-randomized trial conducted largely in parallel with Phase 2 Initial approval based on platelet aggregation biomarker SAD: healthy subjects BLA US Approval Clinical Studies BLA enabling data Phase 1 ✔ Major Bleeding and Urgent Surgery Phase 3 Ph2b: ~200 healthy older subjects Phase 2 FDA Interim analysis for BLA submission Ph2a: healthy older subjects

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Continued Long Term Unit Growth of Ticagrelor Fueled by PB2452 approval Brilinta/Brilique sales in 2018 were $1.32B and growing (+22% Y/Y) Patient growth drives Y/Y revenue growth in all regions: EU (+18%), US (+16%), Emerging Markets (+46%) In February 2019, Brilinta Phase III THEMIS1 trial met primary endpoint in patients with established coronary artery disease and type-2 diabetes Brilinta Phase III THALES2 trial in stroke expected to readout in 2020 Ticagrelor Differentiation vs. clopidogrel Efficacy ✔ ✔ ✔ Safety -- (no reversal agent) ✔ ✔ Price O (branded vs. generic) O (branded vs. generic) ✔ Now Post PB2452 Launch Post LOE of ticagrelor https://www.astrazeneca.com/media-centre/press-releases/2019/brilintas-phase-iii-themis-trial-met-primary-endpoint-in-patients-with-established-coronary-artery-disease-and-type-2-diabetes-25022019.html https://clinicaltrials.gov/ct2/show/study/NCT03354429 Copyright © 2019 PhaseBio Pharmaceuticals, Inc. All Rights Reserved

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PB2452 Program Summary and Next Steps Phase 1 trial achieved clinically-important immediate and sustained reversal of ticagrelor Well tolerated and no PB2452-related SAEs Product profile: Immediate and sustained reversal of ticagrelor antiplatelet effects Major bleeding requires immediate and sustained reversal Duration of reversal dependent on infusion length Next steps for program Phase 2a study to confirm most appropriate dose and dose regimen in healthy older subjects Initiation of large Phase 2b study to support BLA safety database

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Elastin-Like Polypeptide Technology (ELP) – Engine for Growth

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PROLONGED CIRCULATING HALF-LIFE Repeating Sequence of Human Elastin Peptides VPGXG Peptide/Protein (VIP, GLP1, etc.) Active Moiety “Biopolymer” n UP TO 200x INCREASE IN ½ LIFE Proprietary Elastin-Like Polypeptide (ELP) Technology Growth Engine for PhaseBio Preclinical Pipeline ↑ Temperature COACERVATION DELIVERS SLOW RELEASE Inside Body Non-Soluble ELP WEEKLY OR MONTHLY DOSING Outside Body Highly Soluble ELP Pharmacokinetics Slower rate of bioavailability Ease of Administration Patient Compliance IMPROVING

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ELP: A Highly Flexible Technology for Modulating Pharmacokinetics VERSATILE: MANY ACTIVE MOIETIES POSSIBLE Peptides or proteins can be genetically fused to N- or C-terminus1, or both. Chemical conjugation to small molecules or peptides LOW COST MANUFACTURING Can be produced in E.coli, yeast or mammalian cells FLEXIBLE EXPOSURE ELP engineering enables exposures ranging from weekly or monthly to rapid uptake (e.g. prandial insulin) WELL TOLERATED Well characterized across multiple clinical programs CORE ELP TECHNOLOGY https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3622222/

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PB1046 - Once Weekly Vasoactive Intestinal Peptide (VIP) Analog for Pulmonary Arterial Hypertension

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High Unmet Need in an Orphan Disease Primary Pulmonary Arterial Hypertension (PAH, WHO Group 1 PH) High unmet need for novel disease-modifying PAH therapies for greater efficacy All 3 approved drug classes in PAH are vasodilators: prostacyclin, endothelin, and nitric oxide pathways Patients inevitably continue to decline and die on standard of care VIP addresses PAH vasoconstriction, progressive vascular remodeling, and right heart failure McGlaughlin et al. (2015) J. Am. Coll. Cardiol., 65:18

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PB1046: Harnessing VIP to Create a Stable, Long-Acting Drug PRECLINICAL STUDIES Support Clinical Development for: Pulmonary Arterial Hypertension DMD Cardiomyopathy Heart Failure (Chemotherapy-Induced HF or HFpEF) Cystic Fibrosis MECHANISM OF ACTION VIA VPAC2 RECEPTOR Potent vasodilator Anti-inflammatory and anti-fibrotic Cardiac support through increased inotropy and lusitropy VIP as a THERAPEUTIC AGENT VPAC2 VPAC1 Half-Life ~60 Hours in Humans PB1046 VPAC2 VPAC1 VIP Peptide Half-Life ~ 1 minute in Humans

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PHASE 1 Studies Completed PAH PHASE 2 Studies Well tolerated for a week over broad range of exposure; no drug-related SAEs Prolonged PK/PD profile over 1 week VIP activity confirmed (Systolic and Diastolic BP lowering) Well tolerated across dose range; no drug-related SAEs Replicated PK/PD from SAD over 4 weekly SC injections VIP activity reproduced in HFrEF patients on SOC COMPLETED COMPLETED SAD study in HTN patients washed off meds 4-week MAD study in HFrEF patients on SOC PB1046 Clinical Development Activities to Date Have Supported Advancement into a Phase 2b PAH Efficacy Study Open-Label Phase 2a CardioMEMS in PAH study: Safety and Hemodynamics Phase 2b PAH Efficacy 16-Wk Randomized, Controlled Study PHASE 2b STUDY ACTIVELY ENROLLING CardioMEMS Open-Label PAH Study N = 3 patients, dosed weekly for 8 wks, followed by extension No longer enrolling patients Realtime PA pressure and other hemodynamic monitoring Initial data show improved hemodynamics One drug-related SAE reported in extension portion of open-label pilot study Phase 2b PAH 16 wk randomized, controlled study N = ~60 class II/III PAH patients, dosed weekly x 16 weeks Individual dose titration to MTD Efficacy endpoints PVR via RHC, 6MWD Extension study to follow COMPLETED

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PB1046 Single Ascending Dose Study PK and PD Support Once-Weekly SC Administration Single subcutaneous injections in hypertensive patients washed off medications Well tolerated, week-long PK, dose-dependent VIP activity observed Supports weekly SC dosing in multi-dose studies Serum Concentration PB1046 (ng/mL) Slow Release Kinetics (Tmax 48 h) PK HALF-LIFE ~60 HOURS VIP EFFECT ON SYSTOLIC BLOOD PRESSURE Restart Background Anti-hypertensive Therapy 14 21 28

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PB1046 Multiple Ascending Dose Study Multi-Dose Safety and PK/PD Confirmed in HFrEF Patients MAD in HFrEF completed 4Q2017 Weekly SC injections x 4 weeks in 29 HF patients maintained on SOC meds Well tolerated in a sick patient population on multiple vasoactive medications Prolonged PK profile replicated in heart failure patients Dose-related systolic BP reduction confirms durable VIP activity PB1046 Induced Sustained Reduction in Systolic BP p = 0.043, placebo vs PB1046 1.2 mg/kg

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PB1046 Phase 2b PAH Study Actively Recruiting PAH WHO functional class II/III subjects on two drug oral SOC therapy 16 week randomized, double-blinded, controlled study with extension Primary endpoints: Pulmonary vascular resistance (PVR) via RHC, 6MWD, safety Designed to support placebo-controlled Phase 3 registrational study PhaseBio awarded NIH/NHLBI SBIR R44 grant to support PAH program $2.8M award supports CardioMEMS and Phase 2b PAH studies Open-label extension PB1046 individually titrated to Maximum Tolerated Dose Weekly SC injection x 16 weeks PB1046 Minimum Effective Dose with mock dose titration Weekly SC injection x 16 weeks

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phas-ex992_8.htm

Exhibit 99.2

 

 

PhaseBio Announces Proposed Public Offering of Common Stock

 

MALVERN, Pa., and SAN DIEGO, April 9, 2019 (GLOBE NEWSWIRE) — PhaseBio Pharmaceuticals, Inc. (Nasdaq: PHAS), a clinical-stage biopharmaceutical company focused on the development and commercialization of novel therapies for orphan diseases, today announced that it has commenced an underwritten public offering of 3,000,000 shares of its common stock.  All of the common stock to be sold in the offering will be offered by PhaseBio.  In addition, PhaseBio expects to grant the underwriters a 30-day option to purchase up to an additional 450,000 shares of common stock at the public offering price, less underwriting discounts and commissions. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or the actual size or terms of the offering. 

Citigroup, Cowen and Stifel are acting as joint book-running managers for the offering. Needham & Company is acting as co-manager for the offering.

The offering will be made only by means of a prospectus. A copy of the preliminary prospectus related to the offering may be obtained from Citigroup Global Markets Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, telephone: 1-800-831-9146; or Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attn: Prospectus Department, telephone: 1-631-274-2806, or fax: 1-631-254-7140.

A registration statement relating to these securities has been filed with the Securities and Exchange Commission but has not yet become effective. These securities may not be sold nor may offers to buy these securities be accepted prior to the time that the registration statement becomes effective. This press release shall not constitute an offer to sell or the 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.

Forward-Looking Statements

This press release contains certain forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including statements with regard to PhaseBio’s proposed securities offering. Words such as “anticipates,” "believes," “expects,” "intends," "projects," "anticipates," and "future" or similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to the inherent uncertainties in predicting future results and conditions and no assurance can be given that the proposed securities offering discussed above will be consummated on the terms described or at all. Completion of the proposed offering and the terms thereof are subject to numerous factors, many of which are beyond the control of PhaseBio, including, without limitation, market conditions, failure of customary closing conditions and the risk factors and other matters set forth in PhaseBio’s Annual Report on Form 10-K for the year ended December 31, 2018 and other filings PhaseBio makes with the SEC from time to time. PhaseBio undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

 

 

 


 

Investor Contact:
John Sharp

PhaseBio Pharmaceuticals, Inc.

Chief Financial Officer

(610) 981-6506

john.sharp@phasebio.com

Media Contact:
Sarah Hall
6 Degrees
(215) 313-5638
shall@6degreespr.com