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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): November 15, 2021
___________________________________
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 including zip code of principal executive offices)

(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))

Securities registered pursuant to Section 12(b) of the Act.
Title of each class
Trading Symbol(s)
Name of exchange on which registered
Common Stock, par value $0.001 per share
PHAS
The Nasdaq Stock Market LLC

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 7.01. Regulation FD Disclosure.

On November 15, 2021, PhaseBio Pharmaceuticals, Inc. (the “Company”) issued a press release entitled “PhaseBio Announces Interim Results from Pivotal REVERSE-IT Phase 3 Trial of Bentracimab for the Reversal of Antiplatelet Effects of Ticagrelor in Patients Requiring Urgent Surgery or Experiencing Uncontrolled Major or Life-Threatening Bleeding.” The full text of the press release (the “Press Release”) is attached as Exhibit 99.1 to this Current Report on Form 8-K.

Also on November 15, 2021, Deepak L. Bhatt, MD, MPH, Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital and professor at Harvard Medical School, gave a presentation regarding the interim analysis from its ongoing REVERSE-IT Phase 3 clinical trial of ticagrelor at the 2021 American Heart Association Scientific Sessions. The presentation is attached as Exhibit 99.2 to this Current Report on Form 8-K.

The information in this Item 7.01 of this Current Report on Form 8-K, including Exhibits 99.1 and 99.2, is being furnished pursuant to Item 7.01 and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (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 of 1933, as amended, or the Exchange Act, whether made before or after the date hereof, except as expressly set forth by specific reference in such filing to this item of this report.

Item 8.01. Other Events.

On November 15, 2021, the Company issued the Press Release announcing the data from a pre-scheduled interim analysis from its ongoing REVERSE-IT Phase 3 clinical trial of ticagrelor.

REVERSE-IT is a Phase 3, multi-center, open-label, prospective single-arm trial designed to study reversal of the antiplatelet effects of ticagrelor with bentracimab in patients who present with uncontrolled major or life-threatening bleeding or who require urgent surgery or invasive procedure.

The prespecified interim analysis of 150 enrolled patients (142 of whom enrolled requiring urgent surgery or an invasive procedure and eight of whom enrolled with uncontrolled major or life-threatening bleeding) demonstrated that bentracimab achieved the primary endpoint of the trial by immediately and sustainably reversing the antiplatelet effects of ticagrelor. As measured by the point-of-care VerifyNow® PRUTest® platelet function assay (“VerifyNow”), a 135% reduction in platelet inhibition (P<0.001) was observed within five to ten minutes after initiation of bentracimab infusion and sustained through all timepoints over 24 hours. More than 90% of eligible patients achieved the co-primary endpoint of the trial, defined as good or excellent hemostasis within 24 hours of initiation of bentracimab therapy (P<0.001). Thrombotic events were reported in 5.3% of patients, with none resulting in death or considered by investigators to be related to bentracimab. Bentracimab was generally well tolerated, with only five non-serious adverse events, reported in three patients, considered by investigators to be related to bentracimab. The most common adverse events were related to pain associated with surgical procedures.

REVERSE-IT Interim Results Detail

Ticagrelor Reversal Endpoint

The primary ticagrelor reversal endpoint in the REVERSE-IT trial, the minimum percent inhibition of P2Y12 reactivity units (“PRU”) within four hours of bentracimab initiation, was assessed using VerifyNow by measuring the difference in PRU inhibition before the initiation of bentracimab infusion and up to four hours after initiation of bentracimab infusion. Per the prespecified analysis plan, patients with pre-treatment PRU in the normal range (>180) were excluded from reversal assessments, with adjudication resulting in the inclusion of 129 patients in the reversal efficacy analysis. A 135% reduction in inhibition was observed with bentracimab, indicating achievement of the primary reversal endpoint (P<0.001). PRU measured at multiple timepoints rose from a mean of 65 PRU before bentracimab administration to 230 PRU within five to ten minutes after initiation of bentracimab infusion and remained between 230 and 300 PRU through 24 hours after initiation of infusion (P<0.001 across all timepoints). All prespecified subgroups, including the bleeding subgroup, exhibited similar, statistically significant reductions in PRU inhibition.

Clinical Hemostasis Endpoint

The co-primary endpoint for the trial is achievement of effective hemostasis in the overall study population as adjudicated by an independent Clinical Endpoints Committee (“CEC”). The hemostasis endpoint was defined using prespecified efficacy criteria adapted from the Global Use Strategies for Opening Occluded Coronary Arteries ("GUSTO") bleeding scale and a clinical trial of andexanet alpha for surgical and bleeding patients, respectively. The CEC adjudicated hemostasis in a total of 122 patients determined to have met eligibility criteria and found that 98.4% (P<0.001) achieved effective hemostasis within 24 hours of initiation of bentracimab infusion.




Safety Results and Immunogenicity

Safety results were assessed in all 150 patients who were treated with bentracimab and followed for 35 days after enrollment in the trial. Treatment emergent adverse events (“TEAEs”) were reported in 91% of enrolled patients; the most common TEAE was pain associated with surgical procedures. Cardiac and metabolic disorders, such as atrial fibrillation, sinus tachycardia, and electrolyte abnormalities, were also common. Four patients died of events considered by investigators to be unrelated to treatment with bentracimab: two patients from septic shock and two patients from cardiogenic shock. Five adverse events, reported in three patients, were considered by investigators to be potentially related to treatment with bentracimab, and none were considered to be serious adverse events (“SAEs”). The adverse events considered related to treatment with bentracimab included infusion site bruising (0.7%), infusion site warmth (0.7%), bundle branch block (1.4%) and catheter-related jugular thrombosis (0.7%). Bentracimab immunogenicity was also measured in the trial by testing patients for anti-drug antibodies (“ADA”) before and after the initiation of bentracimab infusion. Results of the immunogenicity testing found that 22.6% of patients had pre-existing ADA, 24.3% of patients developed ADA after bentracimab infusion, and 53.0% of patients had no ADA. The presence of ADA had no apparent effect on ticagrelor reversal as measured by VerifyNow or on achievement of effective hemostasis.

Thrombotic Events and Assessment of Potential Prothrombotic Rebound

Eight of the 150 bentracimab-treated patients (5.3%) reported SAEs determined to be thrombotic events, although none resulted in death, and none were considered by investigators to be related to treatment with bentracimab. An assessment of whether bentracimab induced potentially prothrombotic changes in platelet activity was also conducted. Biomarkers of platelet activation, including circulating P-selectin and mean platelet volume, were measured prior to bentracimab initiation and at multiple timepoints following the infusion of bentracimab. Neither biomarker changed after the infusion of bentracimab compared with pre-dose levels, indicating that bentracimab did not show signs of a prothrombotic rebound effect. Taken together, the platelet biomarker analyses, and the relatively low number of thrombotic events seen in this trial, suggest that the risk of a post-reversal prothrombotic rebound effect on platelets is low.

Item 9.01 Financial Statements and Exhibits.
 
(d)    Exhibits
Exhibit No. Description
99.1
99.2
104Cover page interactive data file (formatted as Inline XBRL).






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: November 15, 2021By:/s/ John P. Sharp
John P. Sharp
Chief Financial Officer



Document

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PhaseBio Announces Interim Results from Pivotal REVERSE-IT Phase 3 Trial of Bentracimab for the Reversal of Antiplatelet Effects of Ticagrelor in Patients Requiring Urgent Surgery or Experiencing Uncontrolled Major or Life-Threatening Bleeding

Global Phase 3 trial of bentracimab achieved primary reversal endpoint with immediate and sustained reversal of the antiplatelet effects of ticagrelor in both surgical and bleeding populations

Co-primary endpoint of clinical hemostasis achieved in greater than 90% of patients

Bentracimab appeared well tolerated with no drug-related serious adverse events

Results presented today in Late-Breaking Science Session at the American Heart Association’s 2021 Scientific Sessions and accepted for publication in NEJM Evidence, a new digital journal from the NEJM (New England Journal of Medicine) Group

Investor webcast scheduled for today at 12:30 p.m. ET

Malvern, PA and San Diego, CA, November 15, 2021PhaseBio Pharmaceuticals, Inc. (Nasdaq: PHAS), a clinical-stage biopharmaceutical company focused on the development and commercialization of novel therapies for cardiopulmonary diseases, in conjunction with its financing and co-development partner for the European Union and China, SFJ Pharmaceuticals, today announced interim results from REVERSE-IT (Rapid and SustainEd ReVERSal of TicagrElor – Intervention Trial). REVERSE-IT is PhaseBio’s ongoing pivotal Phase 3 trial designed to study the reversal of the antiplatelet effects of ticagrelor with lead product candidate bentracimab in patients who present with urgent surgery or an invasive procedure or experiencing uncontrolled major or life-threatening bleeding.

The prespecified interim analysis of 150 enrolled patients (142 of whom enrolled requiring urgent surgery or an invasive procedure and eight of whom enrolled with uncontrolled major or life-threatening bleeding) demonstrated that bentracimab achieved the primary endpoint of the trial by immediately and sustainably reversing the antiplatelet effects of ticagrelor. As measured by the point-of-care VerifyNow® PRUTest® platelet function assay (VerifyNow), a 135% reduction in platelet inhibition (P<0.001) was observed within five to ten minutes after initiation of bentracimab infusion and sustained through all timepoints over 24 hours. More than 90% of eligible patients achieved the co-primary endpoint of the trial, defined as good or excellent hemostasis within 24 hours of initiation of bentracimab therapy. Thrombotic events were reported in 5.3% of patients, with none resulting in death or considered by investigators to be related to bentracimab. Bentracimab was generally well tolerated, with only five non-serious adverse events, reported in three patients, considered by investigators to be related to bentracimab. The most common adverse events were related to pain associated with surgical procedures.




The results were presented today by Deepak L. Bhatt, M.D., M.P.H., Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital and professor at Harvard Medical School, during a Late-Breaking Science Session at the 2021 American Heart Association Scientific Sessions and have been accepted for publication in NEJM Evidence, a new digital journal from the NEJM (New England Journal of Medicine) Group.

“With no approved reversal agents for oral P2Y12 inhibitors, patients who are prescribed these medications to reduce the risk of cardiac events are at increased risk for spontaneous major bleeding events, and physicians are faced with a complex dilemma of balancing bleeding risk and thrombotic risk, should these patients require urgent surgery,” said Dr. Deepak L. Bhatt. “The emerging safety and efficacy profile of bentracimab is quite compelling based on these prespecified interim data from the REVERSE-IT trial presented today, and if approved, bentracimab has the potential to become an important tool in the management of patients who could benefit from ticagrelor therapy.”

Cardiovascular disease remains a leading cause of mortality globally. Orally-administered P2Y12 inhibitors, including ticagrelor, continue to be the mainstay of pharmacotherapy in patients diagnosed with acute coronary syndrome, coronary artery disease and other common cardiovascular diseases because of their demonstrated efficacy in preventing thrombotic events such as myocardial infarction and ischemic stroke. However, hospital admissions of patients on P2Y12 inhibitors who require surgery or experience major bleeding events while persistent on their medication remain a significant driver of global healthcare resource utilization. Within the orally-administered P2Y12 inhibitor class, ticagrelor is unique in that it is the only member of the class that can be reversed, creating a potential safety advantage for patients taking ticagrelor should bentracimab be approved.


“The data presented today from the Phase 3 REVERSE-IT trial of bentracimab are a continuation of the favorable results we’ve seen in the Phase 1, Phase 2a and Phase 2b trials that have been completed to date,” said John Lee, M.D., Ph.D., Chief Medical Officer of PhaseBio. “These interim data continue to support the potential of bentracimab to help address a clear unmet need for patients on ticagrelor worldwide who lack an effective reversal agent. Having the ability to immediately restore platelet function, and ultimately achieve hemostasis in patients taking ticagrelor who require urgent surgery or an invasive procedure or experience uncontrolled major or life-threatening bleeding, would be significant for cardiologists, surgeons and, most importantly, patients. Propelled by these pivotal data, we remain on track to submit our planned Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) in mid-2022, as we move one step closer to potentially commercializing bentracimab in the future.”

REVERSE-IT Interim Results Detail

Ticagrelor Reversal Endpoint
The primary ticagrelor reversal endpoint in the REVERSE-IT trial, the minimum percent inhibition of P2Y12 reactivity units (PRU) within four hours of bentracimab initiation, was assessed using VerifyNow by measuring the difference in PRU inhibition before the initiation of bentracimab infusion and up to four hours after initiation of bentracimab infusion. Per the prespecified analysis plan, patients with pre-treatment PRU in the normal range (>180) were excluded from reversal assessments, with adjudication resulting in the inclusion of 129 patients in the reversal efficacy analysis. A 135% reduction in inhibition was observed with bentracimab, indicating achievement of the primary reversal endpoint (P<0.001). PRU measured at multiple timepoints rose from a mean of 65 PRU before bentracimab administration to 230 PRU within five to ten minutes after initiation of bentracimab infusion and remained between 230 and 300 PRU through 24 hours after initiation of infusion (P < 0.001 across all timepoints). All prespecified subgroups, including the bleeding subgroup, exhibited similar, statistically significant reductions in PRU inhibition.




Clinical Hemostasis Endpoint
The co-primary endpoint for the trial is achievement of effective hemostasis in the overall study population as adjudicated by an independent Clinical Endpoints Committee (CEC). The hemostasis endpoint was defined using prespecified efficacy criteria adapted from the Global Use Strategies for Opening Occluded Coronary Arteries (GUSTO) bleeding scale and a clinical trial of andexanet alpha for surgical and bleeding patients, respectively. The CEC adjudicated hemostasis in a total of 122 patients determined to have met eligibility criteria and found that 98.4% (P<0.001) achieved effective hemostasis within 24 hours of initiation of bentracimab infusion.

Safety Results and Immunogenicity
Safety results were assessed in all 150 patients who were treated with bentracimab and followed for 35 days after enrollment in the trial. Treatment emergent adverse events (TEAEs) were reported in 91% of enrolled patients; the most common TEAE was pain associated with surgical procedures. Cardiac and metabolic disorders, such as atrial fibrillation, sinus tachycardia, and electrolyte abnormalities, were also common. Four patients died of events considered by investigators to be unrelated to treatment with bentracimab: two patients from septic shock and two patients from cardiogenic shock. Five adverse events, reported in three patients, were considered by investigators to be potentially related to treatment with bentracimab, and none were considered to be serious adverse events (SAEs). The adverse events considered related to treatment with bentracimab included infusion site bruising (0.7%), infusion site warmth (0.7%), bundle branch block (1.4%) and catheter-related jugular thrombosis (0.7%). Bentracimab immunogenicity was also measured in the trial by testing patients for anti-drug antibodies (ADA) before and after the initiation of bentracimab infusion. Results of the immunogenicity testing found that 22.6% of patients had pre-existing ADA, 24.3% of patients developed ADA after bentracimab infusion, and 53.0% of patients had no ADA. The presence of ADA had no apparent effect on ticagrelor reversal as measured by VerifyNow or on achievement of effective hemostasis.

Thrombotic Events and Assessment of Potential Prothrombotic Rebound
Eight of the 150 bentracimab-treated patients (5.3%) reported SAEs determined to be thrombotic events, although none resulted in death, and none were considered by investigators to be related to treatment with bentracimab. An assessment of whether bentracimab induced potentially prothrombotic changes in platelet activity was also conducted. Biomarkers of platelet activation, including circulating P-selectin and mean platelet volume, were measured prior to bentracimab initiation and at multiple timepoints following the infusion of bentracimab. Neither biomarker changed after the infusion of bentracimab compared with pre-dose levels, indicating that bentracimab did not show signs of a prothrombotic rebound effect. Taken together, the platelet biomarker analyses, and the relatively low number of thrombotic events seen in this trial, suggest that the risk of a post-reversal prothrombotic rebound effect on platelets is low. Completion of the trial will provide additional insight into this important question.

REVERSE-IT Clinical Program
The REVERSE-IT trial is expected to enroll approximately 200 major bleeding or urgent surgery patients at sites in the United States, Canada, the European Union and China. Based on prior guidance from the FDA, to balance the two patient populations, the REVERSE-IT trial does not allow enrollment of more than approximately two-thirds of either the uncontrolled major or life-threatening bleeding population or urgent surgery or invasive procedure population. Because the total number of patients enrolled in the prespecified interim analysis included 142 patients who required urgent surgery or an invasive procedure, PhaseBio has determined that the surgery cohort of the trial has been fully enrolled. With the successful completion of enrollment in this surgery cohort, REVERSE-IT trial sites have shifted focus to enrolling patients with uncontrolled major or life-threatening bleeding events. PhaseBio is seeking to accelerate enrollment of patients with uncontrolled major or life-threatening bleeding, including by working to increase the number of enrolling clinical trial sites as it believes that a broader site footprint will increase the probability of enrolling these patients. The FDA also previously indicated that an interim analysis of



the first approximately 100 patients enrolled in the REVERSE-IT trial would be sufficient to support the submission of a BLA for accelerated approval of bentracimab. The FDA recommended that the 100 patients comprising the interim analysis include approximately 50 patients from each of the major or life-threatening bleeding population and urgent surgery or invasive procedure population, although the FDA noted that whether there are an adequate number of patients from either cohort would be a review issue and considered in the context of other data submitted with the BLA. PhaseBio is commencing preparation of the BLA and is targeting a BLA submission to the FDA in mid-2022.

Bentracimab has been studied in Phase 1 and Phase 2 clinical trials and demonstrated immediate and sustained reversal of the antiplatelet activity of ticagrelor. If these data are reproduced in the final results from the Phase 3 study, bentracimab may have the potential to bring life-saving therapeutic benefit to patients by potentially mitigating concerns regarding bleeding risks associated with the use of ticagrelor. Additionally, in a translational study, bentracimab achieved equivalent reversal of branded ticagrelor and multiple ticagrelor generics.

Investor Event Webcast Information
Members of the PhaseBio senior management team will review these new interim results during a conference call and live video webcast today at 12:30 p.m. ET (9:30 a.m. PT) following the late-breaking science session. The PhaseBio management team will be joined by the following key opinion leaders:

Deepak L. Bhatt, M.D., MPH, Executive Director of Interventional Cardiovascular Programs, Brigham and Women's Hospital and Professor of Medicine at Harvard Medical School

Charles Pollack, M.D., MA, FACEP, Clinician-Scientist, Department of Emergency Medicine, University of Mississippi Medical Center in Jackson

Ph. Gabriel Steg, M.D., FESC, FACC, Interventional Cardiologist and Chief of Cardiology of Hôpital Bichat in Paris, France and Professor of Cardiology at University of Paris

To access the live and subsequently archived webcast, go to the Investor Relations section of PhaseBio's website at https://investors.phasebio.com. Interested parties may RSVP to join the virtual event through the following registration link: https://onlinexperiences.com/Launch/QReg/ShowUUID=19CB5A76-2767-43C6-A132-B025301158EB. The webcast can also be accessed by phone by calling 833-942-2359 from the United States and Canada or 470-414-9401 internationally and using the conference ID/passcode 5616009.


About Bentracimab (PB2452)
Bentracimab is a novel, recombinant, human monoclonal antibody antigen-binding fragment designed to reverse the antiplatelet activity of ticagrelor in major bleeding and urgent surgery situations. In a Phase 1 clinical trial, bentracimab demonstrated the potential to bring life-saving therapeutic benefit through immediate and sustained reversal of ticagrelor’s antiplatelet activity, mitigating concerns regarding bleeding risks associated with the use of this antiplatelet drug. Data from the Phase 1 clinical trial of bentracimab in healthy volunteers was published in the New England Journal of Medicine in March 2019. In April 2019, bentracimab received Breakthrough Therapy Designation from the FDA. In September 2019, PhaseBio completed a Phase 2a trial in which bentracimab was investigated in healthy, older and elderly subjects on dual antiplatelet therapy of ticagrelor and low-dose aspirin. Additionally, the Phase 2a trial investigated a bentracimab regimen for the reversal of supratherapeutic doses of ticagrelor in healthy younger subjects. In November 2021, PhaseBio completed a Phase 2b trial in which bentracimab was investigated in healthy, older and elderly subjects on dual antiplatelet therapy of ticagrelor and low-dose aspirin. In all active treatment arms in both the Phase 2a and Phase 2b trials, bentracimab achieved



immediate and sustained reversal of the antiplatelet effects of ticagrelor and was generally well-tolerated, with only minor adverse events reported. These results are consistent with the results observed in healthy younger subjects treated with ticagrelor in the previously published Phase 1 trial. PhaseBio initiated REVERSE-IT, a pivotal Phase 3 clinical trial of bentracimab, in March 2020 to support a potential Biologics License Application for bentracimab in both major bleeding and urgent surgery indications.


About PhaseBio
PhaseBio Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on the development and commercialization of novel therapies for cardiovascular and cardiopulmonary diseases. PhaseBio’s pipeline includes: bentracimab (PB2452), a novel reversal agent for the antiplatelet therapy ticagrelor; pemziviptadil (PB1046), a once-weekly vasoactive intestinal peptide (VIP) receptor agonist for the treatment of pulmonary arterial hypertension; and PB6440, an oral agent for the treatment of resistant hypertension. PhaseBio’s proprietary elastin-like polypeptide technology platform enables the development of therapies with potential for less-frequent dosing and improved pharmacokinetics, including pemziviptadil, and drives both internal and partnership drug-development opportunities.

PhaseBio is located in Malvern, PA, and San Diego, CA. For more information, please visit www.phasebio.com, and follow us on Twitter @PhaseBio and LinkedIn.

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “anticipates,” “believes,” “expects,” “intends,” “potential,” “projects,” “target,” “will,” “would” and “future” or similar expressions are intended to identify forward-looking statements.

Forward-looking statements include statements concerning or implying the conduct or timing of our clinical trials and our research, development and regulatory plans for our product candidates, the timing of availability or disclosure of data from those clinical trials and the timing of planned regulatory submissions, the potential for these product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies, and whether, if approved, these product candidates will be successfully distributed, marketed and commercialized. Forward-looking statements are based on management's current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements.

Risks regarding our business are described in detail in our Securities and Exchange Commission filings, including in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2021. These forward-looking statements speak only as of the date hereof, and PhaseBio Pharmaceuticals, Inc. disclaims any obligation to update these statements 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:
Will Zasadny
Canale Communications, Inc.
(619) 961-8848
will.zasadny@canalecomm.com


a20211114-ahareversexiti
REVERSE-IT Phase 3 Trial: Interim Results Presentation and Roundtable Discussion November 15, 2021


 
Introduction and Corporate Update Jonathan Mow Chief Executive Officer, PhaseBio


 
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,” “target,” “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 Quarterly Report on Form 10-Q for the quarter ended September 30, 2021. 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. Legal Disclaimer 3


 
Program Pre-Clinical Phase 1 Phase 2 Phase 3 Commercial Rights Upcoming Milestone Target2 Bentracimab Reversal of Ticagrelor Antiplatelet Activity November 15, 2021 Topline results from Interim Analysis of REVERSE-IT Pemziviptadil Pulmonary Arterial Hypertension (PAH) Mid 2022 Report Phase 2B data PB6440 Resistant Hypertension 2022 Submit IND and initiate first-in-human clinical trial Partnering Opportunities GLP2-ELP Short Bowel Syndrome CNP-ELP Achondroplasia Early Programs PROPRIETARY LONG-ACTING INJECTABLE RECOMBINANT BIOPOLYMERS (Elastin-like Polypeptides – ELPs) A Clinical Stage, Cardiopulmonary Focused Biopharmaceutical Company 4 REVERSE-IT1 Phase 3 ongoing Targeting to submit BLA in Mid 20222 Phase 2B ongoing2 Late research Late research 1. REVERSE-IT: Rapid and SustainEd ReVERSal of TicagrElor – Intervention Trial 2. Targeted timeline could be impacted by the continued scope and duration of the COVID-19 pandemic Pre-Clinical


 
Why We Are Here Today 5 Bentracimab Clinical Overview • Discuss P2Y12 inhibitor class, bentracimab and unmet need • Review published bentracimab Phase 1 trial results • Preview unpublished data from Phase 2A trial REVERSE-IT Phase 3 Interim Results • Describe trial overview and goals • Review clinical data, key endpoints and safety results from prespecified interim analysis of the REVERSE-IT trial • Contextualize results and key learnings Expert Panel Discussion • Review unmet needs for patients treated with P2Y12 inhibitors • Discuss REVERSE-IT results with world- renowned experts in the fields of cardiology and emergency medicine • Highlight potential for bentracimab to address unmet needs


 
• At the outset of the bentracimab clinical development program, PhaseBio set out criteria for what an ideal ticagrelor reversal agent would look like ⎯ Because it was a theoretical exercise, the bar was set high • Specifically, we aspired to develop a product that was: 1. Safe: patients requiring reversal of ticagrelor are complex and diverse, making safety paramount 2. Specific: ticagrelor reversibly binds to platelets; implementing a reversal strategy to target ticagrelor and its active metabolite provided an opportunity to limit unwanted off-target effects 3. Immediate: clinical scenarios requiring reversal of ticagrelor are time sensitive; immediate onset of action is key 4. Durable: restoration of platelet function for an extended period to ensure achievement of hemostasis prior to resuming an antiplatelet regimen was considered optimal 5. Simple: ease of use with no reconstitution, thawing or other preparation is important when time is of the essence 6. Predictable: a drug works as predicted in a wide variety of clinical settings and does what it is intended to do What We Initially Set Out to Accomplish with the Bentracimab Program 6


 
• Bentracimab delivers immediate and sustained restoration of platelet function in both healthy subjects and in patients requiring urgent surgery or invasive procedure, or experiencing uncontrolled major or life- threatening bleeding events • Results from the interim analysis of the Phase 3 REVERSE-IT trial reflect aspirational target profile: ⎯ Both the primary reversal endpoint and the co-primary hemostasis endpoints have been achieved ⎯ Favorable safety and efficacy profile in both patient cohorts • Safety and efficacy results from the Phase 1, Phase 2A, Phase 2B and Phase 3 trials have been consistent • Based on these results, we believe bentracimab has the potential to become an important tool for physicians to help address clinical scenarios that currently present significant challenges: ⎯ Dilemma of managing thrombotic risk vs. bleeding risk in patients requiring surgery ⎯ Uncontrolled bleeding with no currently-available interventions to help restore platelet function and hemostasis Key Take-Aways 7


 
Discussion Panel Participants 8 Deepak L. Bhatt, MD, MPH Executive Director of Interventional Cardiovascular Programs, Brigham and Women's Hospital and Professor of Medicine at Harvard Medical School Charles Pollack, MD, MA, FACEP Clinician-Scientist, Department of Emergency Medicine, University of Mississippi Medical Center in Jackson Ph. Gabriel Steg, MD, FESC, FACC Interventional Cardiologist and Chief of Cardiology of Hôpital Bichat in Paris, France and Professor of Cardiology at University of Paris


 
Agenda 9 AHA Analyst Call Agenda: November 15th, 12:30pm ET Presenter Time Introductory Remarks Jonathan Mow, PhaseBio Chief Executive Officer 12:30-12:35 Bentracimab Pivotal Program Overview Dr. John Lee, PhaseBio Chief Medical Officer 12:35-12:40 REVERSE-IT AHA Slide Presentation Dr. Bhatt 12:40-12:50 Roundtable Discussion of Results Moderator: Dr. John Lee Key Opinion Leaders: Dr. Bhatt, Dr. Pollack, Dr. Steg 12:50-1:15 Closing Remarks and Analyst Q&A All participants 1:15-1:30


 
Bentracimab Pivotal Program Overview John Lee, MD, PhD Chief Medical Officer, PhaseBio


 
bentracimab Timelines of Bentracimab Program 11 2019 2020 2021 2022 2023 Phase 2B: 50-80 year old volunteersPhase 2APhase 1 NEJM FDA Breakthrough Therapy FDA EOP1 EMA PRIME Designation N=200, 150 randomized to receive bentracimab N=150, major bleeding + urgent surgery patients Final N=200 Post -approval completion of Phase 3 Phase 3 REVERSE-IT trial in ticagrelor patients Targeted BLA Submission Mid -2022 Potential BLA Approval August 2021 Last patient for interim Targeted timelines could be impacted by the continued scope and duration of the COVID-19 pandemic NEJM= New England Journal of Medicine, EOP1=End-of-Phase 1 Meeting, BLA=Biologics License Application Phase 2B study enrollment complete as of August 2021 • Topline results announced in November 2021 • Phase 2B trial designed to supplement safety and efficacy results included in the planned BLA submission Enrollment for interim analysis of REVERSE-IT Phase 3 trial complete • Interim Analysis enrollment complete, with top-line data to be presented on November 15th at AHA • Data from Phase 2B and Phase 3 trials expected to form the basis of a BLA submission for Accelerated Approval • BLA submission currently being prepared and targeted for mid-2022


 
Phase 2B: Reversal of Ticagrelor and Safety Bentracimab achieved primary endpoint of ticagrelor reversal measured by VerifyNow P2Y12 assay • Statistically significant reduction in % inhibition of PRU within 4 hours • Extent of reversal similar to results observed in Phase 1 and 2A studies Safety profile in the Phase 2B study consistent with Phase 1 and 2A studies • No treatment emergent AEs or SAEs considered related to bentracimab • No thrombotic events observed Phase 2B results will be made public at upcoming conference and/or publication


 
REVERSE-IT Phase 3 Trial: Results from Prespecified Interim Analysis Deepak L. Bhatt, MD, MPH Executive Director of Interventional Cardiovascular Programs, Brigham and Women's Hospital and Professor of Medicine at Harvard Medical School


 
REVERSE-IT: Effect of Bentracimab on Platelet Inhibition and Hemostasis in Patients on Ticagrelor with Major Bleeding or Requiring Urgent Procedures Deepak L. Bhatt, MD, MPH, Charles V. Pollack, Jr., MD, C. David Mazer, MD, Dominick J. Angiolillo, MD, PhD, Ph. Gabriel Steg, MD, Stefan K. James, MD, PhD, Jeffrey I. Weitz, MD, Rohit Ramnath, PhD, Susan E. Arnold, PhD, Michael C. Mays, BS, Bret R. Umstead, MS, Barbara White, MD, Lisa L. Hickey, MS, Lisa K. Jennings, PhD, Benjamin J. Curry, PhD, John S. Lee MD, PhD, Subodh Verma, MD, PhD, on Behalf of the REVERSE-IT Investigators


 
Disclosures Dr. Deepak L. Bhatt discloses the following relationships - Advisory Board: Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Novartis, Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Lexicon, Lilly, Medtronic, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Philips, Svelte; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, Takeda. REVERSE-IT is funded by PhaseBio. This presentation discusses off label and investigational uses of drugs.


 
Ticagrelor: Substantial Data, with Broad Label • Ticagrelor is an oral P2Y12 inhibitor that is effective (and FDA- approved) in patients with acute coronary syndromes, prior myocardial infarction, high-risk coronary artery disease, transient ischemic attack, and stroke, based on PLATO,1,2 PEGASUS,3,4 THEMIS,5,6 THEMIS-PCI,5,7 and THALES.8 • As with other antiplatelet drugs, spontaneous major bleeding and bleeding associated with urgent or emergent invasive procedures are concerns. • The antiplatelet effects of ticagrelor cannot be reversed with platelet transfusion. Therefore, a rapid-acting reversal agent would be useful. 1James S, Akerblom A, Cannon CP, et al. Am Heart J. 2009;157:599-605. 5Bhatt DL, Steg PG, et al. Clinical Cardiology 2019; 42: 498-505. 2Wallentin L, Becker RC, Budaj A, et al. N Engl J Med. 2009;361:1045-57. 6Steg PG, Bhatt DL, et al. N Engl J Med. 2019;381:1309-1320. 3Bonaca MP, Bhatt DL, Braunwald E, et al. Am Heart J. 2014;167:437-44. 7Bhatt DL, Steg PG, et al. Lancet. 2019;394:1169-1180. 4Bonaca MP, Bhatt DL, Cohen M, et al. N Engl J Med. 2015;372:1791-800. 8Johnston SC, Amarenco P, et al. N Engl J Med 2020;383:207-217.


 
Ticagrelor: Reversible Mechanism of Action Bhatt DL. Nature Reviews Cardiology. 2009;6:737-38.


 
Bentracimab: An Intravenous Monoclonal Antibody The P2Y12 receptor is activated by adenosine diphosphate (ADP) (A). On platelets, ticagrelor reversibly binds to the P2Y12 receptor. This induces a conformational change which prevents ADP from signaling through to the P2Y12 receptor, inhibiting platelet activation (B). Bentracimab is a recombinant human IgG1 monoclonal antibody fragment which binds to free ticagrelor with high affinity and specificity. This allows ADP to activate platelets while the bentracimab:ticagrelor complex is eliminated from the bloodstream (C and D). Ha ACT, Bhatt DL, Rutka JT, Johnston SC, Mazer CD, Verma S. J Am Coll Cardiol. 2021;78:1372-1384.


 
Immediate Onset and Sustained Duration of Ticagrelor Reversal Using Bentracimab (formerly PB2452) P values by timepoint for each cohort Cohort 5min 0.25h 0.5h 1h 2h 3h 6h 8h 10h 12h 16h 20h 7 0.040 0.040 0.131 0.037 0.040 0.019 0.019 0.019 0.152 0.019 0.019 0.224 8 0.019 0.019 0.019 0.019 0.019 0.019 0.019 0.019 0.152 0.019 0.019 0.019 10 0.043 0.020 0.020 0.020 0.020 0.020 0.020 0.020 N/A 0.020 0.020 0.020 Due to the small sample size for cohort 9 (n=3), statistical testing was not performed. For Cohorts 9 and 10, no 10-hour timepoint was collected. P-values for time point 24 hours or above are not significant. P<0.001 across all timepoints, Bonferroni adjusted LTA= light transmittance aggregometry; ADP is the agonist 1. Immediate and sustained ticagrelor reversal with bolus + prolonged infusion of 18 g bentracimab. 2. Significant reversal was observed 5 minutes after initiation of bentracimab infusion. 3. Duration of reversal was infusion-time dependent, lasting 20-24 hours with a 16-hour infusion. Bhatt DL, Pollack CV, Weitz JI, et al. N Engl J Med. 2019; 380:1825-1833.


 
Bentracimab Phase 2A Data Adverse Events PBO (N=6) Bentracimab (N=17) Any AE – no. 13 20 Subjects with AE – no. (%) 5 (83%) 10 (59%) Dry mouth 1 0 Infrequent bowel movements 1 0 Nausea 1 1 Feeling hot (r) 0 2 Infusion site bruising 1 0 Infusion site erythema 1 0 Infusion site extravasation 0 1 Vessel puncture site bruise 1 4 Bronchitis 0 1 Folliculitis 0 1 Arthropod sting 1 0 Contusion 0 1 ECG T wave inversion (SAE) 0 1 Back pain 1 1 Muscle twitching 0 1 Pain in extremity 0 1 Dizziness (r) 2 1 Dyspnea (r) 0 2 Blood blister 1 0 Macule 0 1 Pruritus 0 1 0 4 8 12 16 20 24 48 PR U 10 0 20 0 30 0 Bentracimab 18 g in 50-80 year-olds with DAPT Time post-dose (hours) -48 PR U Time post-dose (hours) Bentracimab 36 g to reverse ticagrelor 180 BID 10 0 20 0 30 0 0 4 8 12 16 20 24 48 -48 All Treatment Emergent Adverse Events P < 0.001 across all timepoints 5 min - 24 hrs, Bonferroni adjusted P < 0.001 across all timepoints 5 min - 24 hrs, Bonferroni adjusted Bentracimab (N=12) Placebo (N=4) Placebo (N=2) Bentracimab (N=5)


 
REVERSE-IT: Enrollment and Study Flowchart REVERSE-IT Study Design Multicenter, open-label, prospective single-arm study of reversal of the antiplatelet effects of ticagrelor with bentracimab in at least 200 patients who present with uncontrolled major or life-threatening bleeding or who require urgent surgery or invasive procedures. Enrollment is ongoing in North America and Europe. Patients with use of ticagrelor within the prior 3 days who require urgent ticagrelor reversal are eligible for enrollment. Bentracimab was granted Breakthrough Therapy designation by the FDA and PRIME (priority medicines) designation by the European Medicines Agency, and in consultation with them, we performed this prespecified, interim analysis to support a BLA submission for an accelerated (conditional) approval.


 
REVERSE-IT: Endpoints Primary Reversal Endpoint The minimum % inhibition of PRU within 4 hours of bentracimab initiation as assessed by the Verify Now™ PRUTest™ platelet function assay Primary Hemostasis Endpoint (Will be Centrally Adjudicated) Achievement of effective hemostasis within 24 hours after start of PB2452 infusion assessed in each population separately and then pooled for primary endpoint analysis: • Uncontrolled major bleeding: Assessed using prespecified criteria for effective hemostasis for visible and non-visible major bleeding adapted from (Connolly, 2016) • Urgent surgery or invasive procedure: Assessed using prespecified criteria for effective hemostasis derived from GUSTO clinical bleeding scale (GUSTO, 1993)


 
REVERSE-IT Study Committees Steering Committee Deepak L. Bhatt MD, MPH (Chair), Dominick J. Angiolillo, MD, PhD, Stefan K. James, MD, PhD, Charles V. Pollack, Jr., MA, MD, Ph. Gabriel Steg, MD, Subodh Verma, MD, PhD, Jeffrey I. Weitz, MD Data Safety Monitoring Board W. Frank Peacock, MD, (Chair), Denise Ann Esserman, PhD, Sunil Rao, MD, Richard Whitlock, MD, PhD DSMB Management: Louise Gambone Clinical Endpoint Committee Robert P. Giugliano MD, SM (Chair), Marc P. Bonaca, MD, MPH, John W. Eikelboom, MBBS, MS, Eli V. Gelfand, MD, Kenneth W. Mahaffey, MD, Yuri B. Pride, MD, Christian T. Ruff, MD, PhD CEC Management: Susan Marble Gibson, Michelle Fitzpatrick Platelet Core Lab Lisa K. Jennings, PhD, Ben Curry, PhD


 
REVERSE-IT Investigators REVERSE-IT Investigators Mentor Ahmeti, MD, Denis Angoulvant, MD, PhD, Craig Brown, MD, Warren Cantor, MD, Michael Charles, MD, Marc Claeys, MD, PhD, Francesco Franchi, MD, Alex Gregory, MD, Zafir Hawa, MD, Michael Heffernan, MD, John Kotter, MD, Gilles Lemesle, MD, PhD, David Mazer, MD, Shamir Mehta, MD, Marc Ruel, MD, Tarit Saha, MD, Jean- Francois Tanguay, MD, Jurrien M. Ten Berg, MD, PhD, Marco Valgimigli, MD, PhD, Sam Van Boxstael, MD, Philippe Vanduynhoven, MD, Pierre Voisine, MD, Terry Yau, MD


 
REVERSE-IT: Enrollment and Study Flowchart


 
REVERSE-IT: Baseline Characteristics


 
REVERSE-IT: Platelet Function Tests Percent Inhibition of PRU PRU Analysis of Reversal Ticagrelor Reversal with VerifyNow PRU. Ticagrelor reversal is shown as a reduction in % inhibition of PRU or PRI and as an increase in PRU or platelet reactivity index at multiple timepoints post-treatment. Shown is the comparison of % inhibition of PRU pre-treatment and the minimum % inhibition of PRU within 4 hours of initiation of bentracimab infusion (left). Onset and duration of ticagrelor reversal in bentracimab-treated patients observed as an increase in PRU with P value at each timepoint Bonferroni adjusted (right).


 
REVERSE-IT: Platelet Function Tests PRI analysis of ReversalPercent Inhibition of PRI Ticagrelor Reversal with VASP platelet reactivity index (PRI). Comparison of % inhibition of platelet reactivity index pre- treatment and the minimum % inhibition of platelet reactivity index within 4 hours of initiation of bentracimab infusion (left). The onset and duration of ticagrelor reversal in bentracimab-treated patients observed as an increase in platelet reactivity index with P value at each timepoint Bonferroni adjusted (right).


 
REVERSE-IT: Reversal in Surgical and Bleeding Pts PRU analysis in surgical and bleeding patients PRI analysis in surgical and bleeding patients Ticagrelor Reversal in Bleeding and Surgical Patients. Multiple platelet function assays were used to measure extent of ticagrelor reversal in bleeding and surgical patients. Shown is platelet aggregation pre-treatment and at multiple timepoints post initiation of bentracimab in bleeding patients compared to surgical patients as measured by VerifyNow P2Y12 assay (left). The VASP PRI assay was used to assess ticagrelor’s suppression of P2Y12 receptor signaling pre-treatment and at multiple timepoint post-initiation of bentracimab in bleeding vs. surgical patients (right).


 
REVERSE-IT: Platelet Function Tests Subgroups Forest Plot for % Inhibition of PRU Prespecified Subgroup Analyses of the Primary Reversal Endpoint. The primary reversal endpoint was the minimum % inhibition of PRU within 4 hours of study drug initiation compared to pre-treatment % inhibition of PRU. Shown is a Forest plot of the pretreatment % inhibition of PRU compared to the minimum %inhibition within 4 hours of study drug in pre-specified subgroups.


 
Enrollment of Urgent Surgical and Major Bleeding Patients in REVERSE-IT Enrolled Urgent Surgical and Major Bleeding Patients


 
REVERSE-IT: Adjudicated Surgical Hemostasis Adjudicated and Investigator-Reported Surgical Outcomes


 
REVERSE-IT: Adjudicated Bleeding Hemostasis Adjudicated and Investigator-Reported Bleeding Outcomes


 
REVERSE-IT: Adjudicated Hemostasis Subgroups Forest Plot for Effective Hemostasis (Adjudicated) Prespecified Subgroup Analyses of the Primary Hemostasis Endpoint. The primary hemostasis endpoint was the proportion of patients adjudicated to have achieved effective hemostasis compared to 50% expected by the null hypothesis. Shown is a Forest plot of the proportion of patients with effective hemostasis within 24 hours of initiation of bentracimab infusion in pre-specified subgroups


 
REVERSE-IT: No Platelet Rebound Activity P-selectin in surgical and bleeding patients Mean platelet volume in surgical and bleeding patients Effect of Bentracimab Treatment on P-Selectin and Mean Platelet Volume (MPV). Soluble P-selectin and MPV were measured pre-dose and at multiple timepoints post-initiation of bentracimab treatment to assess for a potentially prothrombotic rebound increase in platelet reactivity post-reversal. Shown are the soluble P-selectin levels in surgical and bleeding patients treated with bentracimab (left). MPV was measured in surgical and bleeding patients treated with bentracimab (right).


 
REVERSE-IT: Adjudicated Thrombotic Events Adjudicated Thrombotic Events Occurring Post-Reversal


 
Limitations • There was no control arm, as it was felt to be challenging to randomize to a placebo (as with the NOAC reversal trials). • The majority of surgical patients underwent cardiac surgery, though no reason to think the results don’t apply to other surgeries and invasive procedures. • The number of patients with bleeding in this prespecified interim analysis was low, though surgery is an excellent model of bleeding (and the bleeding subgroup showed statistically significant benefits). • Enrollment of additional patients with bleeding is ongoing.


 
Conclusion • Using the VerifyNow and VASP assays in ticagrelor-treated patients undergoing invasive procedures or with major bleeding, bentracimab, a specific reversal agent for ticagrelor, provided immediate and sustained reversal of ticagrelor’s antiplatelet effects. • Rates of effective hemostasis were adjudicated as good or excellent in >90% of cases, with no drug-related serious adverse events or allergic or infusion-related reactions . • The benefits were consistent in all prespecified subgroups, including those undergoing surgery and with major bleeding. • Bentracimab appears to be a very promising option for ticagrelor reversal.


 
Bentracimab for Ticagrelor Reversal in Patients Undergoing Urgent Surgery Deepak L. Bhatt, MD, MPH, Charles V. Pollack, Jr., MD, C. David Mazer, MD, Dominick J. Angiolillo, MD, PhD, Ph. Gabriel Steg, MD, Stefan K. James, MD, PhD, Jeffrey I. Weitz, MD, Rohit Ramnath, PhD, Susan E. Arnold, PhD, Michael C. Mays, BS, Bret R. Umstead, MS, Barbara White, MD, Lisa L. Hickey, MS, Lisa K. Jennings, PhD, Benjamin J. Curry, PhD, John S. Lee MD, PhD, Subodh Verma, MD, PhD, on Behalf of the REVERSE-IT Investigators A new monthly Digital journal from the New England Journal of Medicine Group. First issue, January, 2022. This accepted article will be posted at https://evidence.nejm.org/ when production is complete.


 
TICAGRELOR IN STABLE CAD AND T2D TREATED WITH ASA www.brighamandwomens.org/heart Deepak L. Bhatt, MD, MPH Executive Director, Interventional Cardiovascular Programs, BWH Heart & Vascular Center; Professor of Medicine, Harvard Medical School Email: DLBhattMD@post.Harvard.edu Twitter: @DLBhattMD Thank You!


 
REVERSE-IT Phase 3 Trial: Prespecified Interim Results Panel Discussion Deepak L. Bhatt, MD, MPH John Lee, MD, PhD Charles Pollack, MD, MA Ph. Gabriel Steg, MD


 
Closing Remarks and Q&A Jonathan Mow Chief Executive Officer, PhaseBio


 
Thank you!