8-K

 

 

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): December 8, 2020

 

 

Harpoon Therapeutics, Inc.

(Exact name of Registrant as Specified in Its Charter)

 

 

 

Delaware   001-38800   47-3458693

(State or Other Jurisdiction

of Incorporation)

 

(Commission

File Number)

 

(IRS Employer

Identification No.)

131 Oyster Point Blvd, Suite 300

South San Francisco, California

  94080
(Address of Principal Executive Offices)   (Zip Code)

(650) 443-7400

(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 each exchange

on which registered

Common stock, par value $0.0001 per share   HARP   Nasdaq Global Select Market

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 8.01

Other Events.

On December 8, 2020, Harpoon Therapeutics, Inc. (the “Company”) issued a press release announcing clinical progress across all four of the Company’s TriTAC® pipeline development programs. On December 8, 2020, the Company also posted a presentation (the “Presentation”) regarding these updates. Copies of the press release and the Presentation are attached hereto as Exhibits 99.1 and 99.2, respectively, and are incorporated herein by reference.

 

Item 9.01

Financial Statements and Exhibits.

(d) Exhibits.

 

Exhibit No.

  

Description

99.1    Press Release, dated December 8, 2020.
99.2    Clinical Pipeline Update Presentation, dated December 8, 2020.


SIGNATURES

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

 

HARPOON THERAPEUTICS, INC.
By:   /s/ Gerald McMahon, Ph.D.
 

Gerald McMahon, Ph.D.

President and Chief Executive Officer

Dated: December 9, 2020

EX-99.1

Exhibit 99.1

 

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FOR IMMEDIATE RELEASE

Harpoon Therapeutics Reports Clinical Progress Across All Four TriTAC® Pipeline Development Programs

HPN424 has shown confirmed partial response in treatment of metastatic castration-resistant prostate cancer in highest fixed dose cohort (160 ng/kg) of continuing Phase 1/2a dose escalation trial

Three of seven patients in highest fixed dose HPN424 cohort have shown PSA reduction

Dose escalation trials advancing for HPN536 and HPN217 with initial data readouts and initiation of expansion cohorts expected in 2021

Management to host clinical update webcast/call today, December 8, 2020, at 8 a.m. ET

SOUTH SAN FRANCISCO, Calif., December 8, 2020—Harpoon Therapeutics, Inc. (NASDAQ: HARP), a clinical-stage immunotherapy company developing a novel class of T cell engagers, today provided a pipeline update and reported a confirmed partial response based on RECIST v1.1 criteria for its most advanced program, HPN424 for the treatment of metastatic castration-resistant prostate cancer (mCRPC). As of December 1, 2020, in the 160ng/kg cohort, which is the highest fixed dose tested to date, 7 patients have been enrolled and one patient has achieved a confirmed partial response. In addition, 3 patients enrolled in this cohort had serum PSA reductions, including one with a reduction of 50% (PSA50). Dose escalation continues in this trial, in the Phase 1/2a clinical trials for HPN536 as a treatment for ovarian cancer and other mesothelin-expressing solid tumors and in the HPN217 Phase 1/2 clinical trial for multiple myeloma. Step dosing is being utilized in all programs to accelerate testing of higher doses. Dosing of the first patient in the Phase 1/2 trial for Harpoon’s fourth TriTAC development program, HPN328, in small cell lung cancer and other DLL3-associated tumors is expected to occur by the end of the year.

”We are pleased to provide a trial update to our shareholders today, as well as outline our expectations for 2021. We have made significant progress in all of our clinical development programs in 2020,” stated Gerald McMahon, Ph.D., President and CEO of Harpoon Therapeutics. “We are excited to report our first confirmed partial response in the continuing dose escalation trial for HPN424, especially in a heavily pretreated patient population with advanced metastatic disease. We are also excited by the potential for multiple data releases in 2021 on all four of our programs, which we believe represent meaningful milestones for our company.”

“We are pleased to report the activity we are seeing with HPN424 in late-stage prostate cancer patients in our highest fixed dose cohort tested to date,” said Natalie Sacks, M.D., Chief Medical Officer of Harpoon. “We are implementing step dosing in all of our programs, which allows rapid escalation to higher doses. We look forward to sharing data from these higher-dose cohorts in 2021.”


Clinical Program Updates

(All data as of December 1, 2020)

Dose escalation continues in Phase 1/2a trial for HPN424 in the treatment of mCRPC. As of the December 1, 2020 data cutoff date, 69 patients have been dosed across 14 cohorts at fixed doses of 1.3 to 160ng/kg and in step dosing cohorts up to 300ng/kg administered as a weekly intravenous infusion. Enrolled patients had a median of 6 prior systemic therapies, and 76% of patients had prior chemotherapy in the metastatic castration-resistant setting. Ten of 44 patients (23%) with treatment start dates at least 6 months ago remained on study treatment for more than 24 weeks.

At the highest fixed dose tested to date, 160ng/kg, one patient out of 7 has experienced a confirmed partial response with tumor lesion reduction of 43%, and 3 of 7 patients have had serum PSA declines from baseline, including one patient with a PSA reduction greater than 50%.

HPN424 was generally well tolerated and cytokine-related adverse events have been manageable. Reported Grade 3 or higher adverse events have included cytokine release syndrome (CRS) (10%), ALT increase (11%) and AST increase (11%). CRS events and transaminitis have been transient and have not resulted in treatment discontinuation. Dose-limiting toxicities (DLTs) have been observed and have not limited escalation. A maximum tolerated dose (MTD) has not been identified. Presentation of Phase 1 data and initiation of an expansion cohort is planned for the first half of 2021. Interim data from this expansion cohort is anticipated by the end of 2021.

HPN536 (mesothelin TriTAC) Phase 1/2a clinical trial continues escalation. Dosing has occurred across 9 fixed-dose cohorts of 6 to 280ng/kg and 1 step dose cohort up to 600ng/kg. Tumor types treated include late-stage ovarian and pancreatic cancers and peritoneal mesothelioma. Enrolled patients had a median of four prior systemic therapies, and 66% of patients had progressive disease as best response to their most recent prior therapy. Pharmacokinetic analysis shows median half-life of more than 70 hours. Among the relapsed/refractory ovarian cancer patients with at least one post-baseline scan, 8 of 12 (67%) patients showed stability of target lesions.

HPN536 appears to be well tolerated. One CRS grade 3 occurred in the absence of dexamethasone premedication treatment. The CRS resolved, and the patient continued on study with dexamethasone premedication. As of December 1, 2020, no DLTs have been observed. Initiation of an expansion cohort is anticipated by the second half of 2021, with a presentation of Phase 1 data by year-end 2021.

Dose escalation for HPN217 (BCMA TriTAC) Phase 1/2 clinical trial progressing rapidly. Relapsed/refractory multiple myeloma patients have been treated across 6 single-patient fixed dose cohorts of 5 to 810µg, reflecting a more than 100-fold increase in dose in 8 months. HPN217 has been well-tolerated, and no DLTs have been observed as of the December 1, 2020 cutoff date. A presentation of interim data is anticipated in 2021, with initiation of a dose expansion cohort in the second half of 2021.

First patient dosing anticipated for HPN328 (DLL3 TriTAC) by the end of 2020. The first site is open and recruiting for the dose escalation portion of this Phase 1/2 clinical trial. In the first cohort, the patients will receive a flat dose of 15µg of HPN328 administered once weekly by intravenous infusion. Eligible patients include small cell lung cancer patients who have relapsed after platinum chemotherapy and patients with other tumors associated with DLL3 expression. Presentation of initial data is planned for the second half of 2021.


Webcast and Conference Call

Harpoon’s management will host a webcast and conference call at 8 a.m. ET / 5 a.m. PT on December 8, 2020. The live call may be accessed by dialing (866) 951-6894 for domestic callers and (409) 216-0624 for international callers with conference ID code number 1388395. A webcast of the live call will be available online in the investor relations section of the Harpoon website at www.harpoontx.com. A replay of the webcast will be available shortly after the event and can be accessed at the same weblink.

About Harpoon Therapeutics

Harpoon Therapeutics is a clinical-stage immunotherapy company developing a novel class of T cell engagers that harness the power of the body’s immune system to treat patients suffering from cancer and other diseases. T cell engagers are engineered proteins that direct a patient’s own T cells to kill target cells that express specific proteins, or antigens, carried by the target cells. Using its proprietary Tri-specific T cell Activating Construct (TriTAC®) platform, Harpoon is developing a pipeline of novel TriTACs initially focused on the treatment of solid tumors and hematologic malignancies. HPN424 targets PSMA and is in a Phase 1/2a trial for metastatic castration-resistant prostate cancer. HPN536 targets mesothelin and is in a Phase 1/2a trial for cancers expressing mesothelin, initially focused on ovarian and pancreatic cancers. HPN217 targets BCMA and is in a Phase 1/2 trial for relapsed, refractory multiple myeloma. HPN328 targets DLL3 and Harpoon plans to initiate a Phase 1/2 trial in the fourth quarter of 2020. Harpoon has also developed a proprietary ProTriTACTM platform, which applies a prodrug concept to its TriTAC platform to create a therapeutic T cell engager that remains inactive until it reaches the tumor. For additional information about Harpoon Therapeutics, please visit www.harpoontx.com.

Cautionary Note on 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 “may,” “will,” “expect,” “plan,” “anticipate,” “target,” “estimate,” “intend” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Harpoon Therapeutics’ expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties that could cause Harpoon Therapeutics’ clinical development programs, future results or performance to differ significantly from those expressed or implied by the forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about the progress, timing, scope, design and anticipated results of clinical trials, the timing of the presentation of data, the association of data with potential treatment outcomes, the development and advancement of product candidates, and the timing of development milestones for product candidates. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during clinical studies, clinical trial site activation or enrollment rates that are lower than expected, unanticipated or greater than anticipated impacts or delays due to COVID-19, changes in expected or existing competition, changes in the regulatory environment, the uncertainties and timing of the regulatory approval process, the risk that initial or interim results from a clinical trial may not be predictive of the final results of the trial or the results of future trials, the risk that trials may be delayed and may not have satisfactory outcomes, and unexpected litigation or other disputes that impede clinical trial progress. Other factors that may cause Harpoon Therapeutics’ actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Harpoon Therapeutics’ filings with the U.S. Securities and Exchange Commission, including the “Risk Factors” sections contained therein. Except as required by law, Harpoon Therapeutics assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.


Contacts:

Harpoon Therapeutics, Inc.

Georgia Erbez

Chief Financial Officer

650-443-7400

media@harpoontx.com

Westwicke ICR

Robert H. Uhl

Managing Director

858-356-5932

robert.uhl@westwicke.com

###

EX-99.2

Exhibit 99.2

 

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Exhibit 99.2 Spearheading Immunotherapies CLINICAL PIPELINE UPDATE DECEMBER 8, 2020


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This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “expect,” “plan,” “anticipate,” “target,” “estimate,” “intend” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Harpoon Therapeutics’ expectations and assumptions as of the date of this presentation. Each of these forward-looking statements involves risks and uncertainties that could cause Harpoon Therapeutics’ clinical development programs, future results or performance to differ significantly from those expressed or implied by the forward-looking statements. Forward-looking statements contained in this presentation include, but are not limited to, statements about the progress, timing, scope, design and anticipated results of clinical trials, the timing of the presentation of data, the association of data with potential treatment outcomes, the development and advancement of product candidates, and the timing of development milestones for product candidates. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during clinical studies, clinical trial site activation or enrollment rates that are lower than expected, unanticipated or greater than anticipated impacts or delays due to COVID-19, changes in expected or existing competition, changes in the regulatory environment, the uncertainties and timing of the regulatory approval process, the risk that initial or interim results from a clinical trial may not be predictive of the final results of the trial or the results of future trials, the risk that trials may be delayed and may not have satisfactory outcomes, and unexpected litigation or other disputes that impede clinical trial progress. Other factors that may cause Harpoon Therapeutics’ actual results to differ from those expressed or implied in the forward-looking statements in this presentation are discussed in Harpoon Therapeutics’ filings with the U.S. Securities and Exchange Commission, including the “Risk Factors” sections contained therein. Except as required by law, Harpoon Therapeutics assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available. Certain information contained in this presentation and statements made orally during this presentation relate to or are based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party studies, publications, surveys and other data to be reliable as of the date of this presentation, we have not independently verified, and make no representations as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of our internal estimates or research and no reliance should be made on any information or statements made in this presentation relating to or based on such internal estimates and research.


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Product Stage of Development 2020 Achieved Target / Indication Candidate Milestones Preclinical Phase 1 Phase 2 Phase 3 HPN424 PSMA / Prostate cancer POC data presented at ASCO MSLN / Ovarian, HPN536 pancreatic and other Interim data disclosed 12/2020 TriTAC solid tumors BCMA / Multiple HPN217 Initiated Phase 1/2 clinical trial myeloma DLL3 / Small cell lung Submitted IND and plan to HPN328 initiate Phase 1/2 study by EOY cancer 2020 Pro HPN601 EpCAM / GI cancers Nominated IND candidate PSMA: Prostate Specific Membrane Antigen MSLN: Mesothelin BCMA: B Cell Maturation Antigen DLL3: Delta-Like Ligand 3


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• Clinical pipeline update – Status of ongoing TriTAC clinical trials – Some initial observations from fixed-dose cohort escalation phase • Focus on emerging interim efficacy data on HPN424 –Confirmed PR observed at highest fixed dose tested • HPN536: Half-life greater than 70 hours • HPN217: More than 100-fold increase in dose in 8 months • Outline expected milestones in 2021 – Full program updates planned for medical conferences in 2021


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Clinical Update HPN424


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Part 1 – Dose Escalation Dose Escalation: Single Patient ï,³ Gr 2 study drug related toxicity Fixed Dose Escalation: 3 + 3 Step Dosing (3 – 6 pts per dose level) Dose Escalation: 3 + 3 (3 – 6 pts per dose level) MTD or recommended Phase 2 dose Part 2 – Dose Expansion 20 pts treated at recommended phase 2 dose determined in Part 1 • Target Population - Metastatic Castration-Resistant ProstateCancer (mCRPC) - Disease progression on the prior systemic regimen - At least two prior systemic therapies approved for mCRPC - Prior chemotherapy allowed, but not required • Trial Design - Key objectives include characterization of safety, pharmacokinetics, and identification of dose for expansion - Tumor assessments performed every 9 weeks and include conventional CT and bone scans and PSA - Additional assessments include cytokines, CTC • Dosing, Administration & Exposure - HPN424 administered once weekly, one-hour IV infusionï,§One cycle is 3 weeks - Starting dose of 1.3ng/kg established by minimally anticipated biological effect level - As of December 1, 2020, 69 patients have been dosed across 14 cohorts - Fixed Dose: 1.3 to 160ng/kg - Step Dose: 100 ng/kg priming dose as first dose 300ng/kg target dose at second dose and thereafter


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Data from clinical database as of December 1, 2020 Age (Years) Median 70 Range 44—91 Race White 53 (77%) Black or African 6 (9%) American Asian 2 (3%) Other / Not reported 8 (12%) ECOG Performance Status 0 33 (48%) 1 36 (52%) PSA (ng/mL) Mean 524 Median 190 Range 0.1—5000 LDH (U/L) Mean 358 Median 235 Range 117—1303 Location of Metastases Bone 56 (81%) Lymph Node 35 (51%) Lung 7 (10%) Liver 6 (9%) Other 9 (13%) Time Since Diagnosis (Years) Mean 8.9 Median 7.5 Range 0.0 – 27.1 Reason for Entering Study PSA Progression 23 (35%) PSA & Clinical Progression 2 (3%) PSA & Radiographic 7 (11%) Progression Radiographic Progression 16 (25%) Unknown 18 (28%) # of Prior Therapies Median (Range) 6 (1 – 15) # of Prior Novel Hormonal Therapies Median (Range) 2 (0 – 3) Prior Chemotherapy (in mCRPC setting) N 50 of 66 (76%) Median (Range) 1 (0 – 3) • Median of 6 prior systemic therapies, median of 2 prior novel hormonal therapies • 76% of patients had prior chemotherapy in metastatic castration-resistant setting


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Data from clinical database as of December 1, 2020 (n=69) Event, n (%) All Grades Grade 3+ Cytokine-Related Adverse Eventsa Chills 42 (61%) 0 (0%) Cytokine Release Syndromeb 40 (58%) 6 (9%) Pyrexia 40 (58%) 0 (0%) Hypotension 22 (32%) 2 (3%) Infusion Related Reaction 18 (26%) 0 (0%) Flushing 12 (17%) 0 (0%) LFTs AST Increase 16 (23%) 10 (14%) ALT Increase 16 (23%) 7 (10%) All Other Adverse Events Fatigue 33 (48%) 3 (4%) Anemia 23 (33%) 9 (13%) Nausea 23 (33%) 0 (0%) Vomiting 19 (28%) 1 (1%) Constipation 15 (22%) 0 (0%) Back Pain 14 (20%) 4 (6%) Decreased Appetite 14 (20%) 0 (0%) Tachycardia 12 (17%) 0 (0%) Arthralgia 10 (14%) 1 (1%) Diarrhea 10 (14%) 0 (0%) Headache 10 (14%) 0 (0%) Insomnia 10 (14%) 0 (0%) Hyponatremia 8 (12%) 3 (4%) Dyspnea 8 (12%) 1 (1%) Dizziness 8 (12%) 0 (0%) Hypoxia 7 (10%) 2 (3%) Pain in Extremity 7 (10%) 1 (1%) Confusional State 7 (10%) 0 (0%) • Grade 3 CRS observed - Transient - Manageable • Transient elevation of liver enzymes observed - Majority in the setting of CRS - No clinical sequelae • DLTs - Gr 3 CRS (n=2) - Gr 3 Elevated lipase (n=1)* - Gr 3 Seizure (n=1)* *previously reported May 2020


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Data from clinical database as of December 1, 2020 • Fifty-nine patients treated across 12 fixed-dose cohorts (1.3 160 ng/kg) • Time on Treatment – Patients average time on treatment > 3 months, and ranges up to 110 weeks – Ten of 44 (23%) patients with treatment start at least 6 months ago have remained on treatment beyond 24 weeks • PSA – Of 49 patients with post-baseline PSA assessments, 11 pts (22%) had PSA declines from baseline ranging from -3.8% to -76% – Includes 3 PSA50, 1 PSA30 • Tumor assessment – Nine of 19 (47%) pts with measurable disease and >1 post-baseline scan remained stable as best response – One patient with confirmed PR (per RECIST v1.1) • Clinical activity at highest fixed dose tested, 160 ng/kg (n=7) – One confirmed PR – 3/7 with PSA reduction


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[Graphic Appears Here] 4 patients experienced Grade 2 CRS, no Grade 3+ CRS observed


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• Patient 057, a 75-year old male, diagnosed January 2002 Baseline Characteristics Patient 057 PSA Values Reason for Study Radiographic L 40 ECOG 1 35 Entry Progression ng/m 30 PSA 39 Location of Lymph Nodes Disease Assessment (ng/mL) Metastases PR PR ADT, LDH (U/L) 147 Prior Therapies bicalutamide, 0 9 18 apalutamide Weeks PR Partial Response • Initiated HPN424 at 160ng/kg • Demonstrated partial response (-32%) at 1st post-baseline scan at Week 9, confirmed PR                (-43%) at Week 18 • Showed 10% PSA decrease from baseline • Remains on study after 20 weeks of treatment


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Target lesion assessment: • Baseline 28mm • Scan at 9 weeks 19mm -32% decrease • Scan at 18 weeks 16mm -43% decrease


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Data from clinical database as of December 1, 2020 • Fifty-nine patients treated across 12 fixed-dose cohorts (1.3 160ng/kg) – Early clinical signals include time on treatment and PSA kinetics • Encouraging clinical activity at highest fixed dose tested (160ng/kg) – 1 patient had confirmed RECIST partial response – Three of 7 (43%) had PSA reduction • Weekly treatment generally well-tolerated – MTD not yet identified • Patients now enrolling at 300ng/kg in step-dose cohort • Anticipate Phase 1 data presentation 1H21 • Preparation to identify dose and patient population for expansion cohort underway – Initiation targeted for 1H21 – Expansion data update by end of year 2021


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Clinical Update HPN536


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Part 1 – Dose Escalation Dose Escalation: Single Patient ï,³ Gr 2 study drug related toxicity Fixed Dose Escalation: 3 + 3 Step Dosing (3 – 6 pts per dose level) Dose Escalation: 3 + 3 (3 – 6 pts per dose level) MTD or recommended Phase 2 dose Part 2 – Dose Expansion 3 Cohorts (Ovarian, Pancreatic and Mesothelioma) ~20 patients per cohort (Simon 2-Stage design) • Target population (dose escalation) - Platinum refractory or platinum resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer - Unresectable, locally advanced or metastatic pancreatic adenocarcinoma progressing on or after frontline treatment - Malignant pleural or peritoneal mesothelioma with epithelioid histology progressing on or after frontline platinum-based chemotherapy • Trial objectives - Assess safety and tolerability at increasing dose levels - Pharmacokinetic and pharmacodynamic data - Evaluate preliminary anti-tumor activity • Dosing, administration - HPN536 administered once weekly, one-hour IV infusion - Starting dose of 6ng/kg established by minimally anticipated biological effect level


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Data from clinical database as of December 1, 2020 Dose Cohort N Tumor Types Treated (ng/kg) 1 6* 1 Ovarian 2 18* 1 Ovarian 3 54* 1 Ovarian 4 68 6 4 Ovarian, 2 Pancreatic 5 90 7 5 Ovarian, 2 Pancreatic 6 120 6 3 Ovarian, 3Pancreatic 7 160 3 1 Ovarian, 2 Pancreatic 8 210 5 1 Peritoneal Meso, 2 Ovarian, 2 Pancreatic 9 280 5 2 Ovarian, 3 Pancreatic Step Dose 1 600 4 1 Peritoneal Meso, 1 Ovarian, 2 Pancreatic Step Dose 2 1200 Open for enrollment Total 39 21 Ovarian, 16 Pancreatic, 2 Peritoneal Meso * No dexamethasone premedication administered at initiation of HPN536 treatment


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Data from clinical database as of December 1, 2020 • Median of 4 prior systemic therapies • 66% of patients had progressive disease as best response to most recent prior therapy Age (Years) Median (Range) 59 (26 – 73) Sex Female 30 (79%) Race White 36 (92%) Asian 2 (5%) Multiple 1 (3%) ECOG Performance Status 0 19 (49%) 1 20 (51%) CA-125 (U/mL) N 12 Median (Range) 138 (15 – 4478) CA19-9 (U/mL) N 14 Median (Range) 1556 (2 – 95088) Time Since Diagnosis (Years) Median (Range) 2.5 (0.4 – 12.8) # of Prior Therapies Median (Range) 4 (1 – 10) Best Response to Most Recent Prior Tx Complete Response 1 (3%) Partial Response 3 (8%) Stable Disease 7 (18%) Progressive Disease 25 (66%) Unevaluable 2 (6%)


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HPN536 Phase 1/2a Dose Escalation Adverse Events (CTCAE v5.0) in >10% of Patients by Grade, Regardless of Relationship Data from clinical database as of December 1, 2020 Event, n (%) All Grades (%) Grade 3+ (%) • 39 patients in safety database Cytokine-mediated Adverse Eventsa Pyrexia 5 (13%) 0 (0%) Chills 3 (8%) 0 (0%) • No DLTs to-date Cytokine Release Syndromeb 1 (3%) 1 (3%) Hypotension 1 (3%) 1 (3%) All Other Adverse Events • 1 event of CRS (Grade 3) occurred Nausea 11 (28%) 1 (3%) Dyspnea at 54ng/kg in the absence of 11 (28%) 1 (3%) Constipation 10 (26%) 0 (0%) dexamethasone premedication; Decreased Appetite 9 (23%) 0 (0%) was Hypokalemia 9 (23%) 2 (5%) Event resolved and patient Abdominal Pain 8 (21%) 1 (3%) successfully re-treated Fatigue 8 (21%) 0 (0%) Abdominal Distension 7 (18%) 1 (3%) • Most frequent AEs include Vomiting 7 (18%) 0 (0%) Dehydration 7 (18%) 0 (0%) dyspnea, abdominal pain, Headache 7 (18%) 0 (0%) constipation Cough 6 (15%) 0 (0%) Peripheral Edema 5 (13%) 0 (0%) Symptoms of underlying disease Back Pain 5 (13%) 1 (3%) Insomnia 5 (13%) 0 (0%) Pulmonary Embolism 5 (13%) 3 (8%) Anemia 4 (10%) 1 (3%) Diarrhea 4 (10%) 0 (0%) a Includes AEs that were reported as concurrent symptoms of the CRS events b CRS Grading according to Lee Criteria, 2014


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Data from clinical database as of December 1, 2020 • Linear kinetics: dose-dependent in Cmax and AUC, dose-independent T1/2, clearance rate, volume of distribution • Overall median T1/2: 70.9 hours, range of 30.6 – 145.8 hrs [Graphic Appears Here]


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[Graphic Appears Here] • 21 ovarian cancer patients enrolled across 10 dose cohorts • Time on treatment ranged from 1+ to 35 weeks • Four of 17 (24%) eligible patients remained on treatment beyond 24 weeks • Eight of 12 (67%) evaluable patients have shown stability of target lesions


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HPN536 Phase 1/2a Dose Escalation: Focus on Ovarian Cancer Data from clinical database as of December 1, 2020 • Patient 029, a 63-year old female, diagnosed in December 2017 with epithelial ovarian cancer Baseline Characteristics Stage IIIC Location of Metastases Lymph Nodes (2) ECOG 1 Reason for Study Entry Progressive Disease 1. Paclitaxel + Carboplatin Histology Serous Prior Therapies 2. Gemcitabine + Carboplatin + Bevacizumab 3. Liposomal Doxorubicin Time on Most Recent Mesothelin H-Score 95 12.1 Weeks Prior Therapy Patient 029 Tumor Assessments on Treatment 0 9 18 27 36 Stable Disease Time on Treatment (Weeks) (RECISTv1.1) • Initiated HPN536 at 120ng/kg • Demonstrated 25% reduction in target lesions at 2nd post-baseline scan, stable disease per RECISTv1.1 • Remains on study after 27 weeks of treatment


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Data from clinical database as of December 1, 2020 • 39 patients enrolled across 9 fixed dose cohorts and 1 step-dose cohort, from 6 to 600ng/kg • Patients now enrolling at 1200ng/kg in step-dose cohort – 600ng/kg cohort under evaluation • Median half-life of 70 hours supports once weekly HPN536 administration • Encouraging profile across fixed doses tested in platinum-refractory/resistant ovarian cancer patients – Treatment well tolerated – Four of 17 eligible patients remained on treatment beyond 6 months – 8 of 12 (67%) evaluable ovarian cancer patients have shown stable target lesions • Anticipate expansion cohort initiation by end of year 2021 • Anticipate Phase 1 data presentation by end of year 2021


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Clinical Update HPN217 and HPN328


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Part 1 – Dose Escalation Dose Escalation: Single Patient ï,³ Gr 2 adverse event Fixed Dose Escalation: 3 + 3 Step Dosing (3 – 6 pts per dose level) Dose Escalation: 3 + 3 (3 – 6 pts per dose level) MTD or recommended Phase 2 dose Part 2 – Dose Expansion Patients treated at the recommended phase 2 dose determined in Part 1 • Target population - Relapsed/Refractory Multiple Myeloma (R/R MM) - Disease progression on the prior systemic regimen - At least three prior therapies including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody • Trial objectives - Assess safety and tolerability at increasing dose levels - Pharmacokinetic and pharmacodynamic data - Evaluate preliminary anti-tumor activity • Dosing and administration - Weekly IV infusion of HPN217 • Trial status - Dose escalation ongoing - US and EU sites open and recruiting - Expect interim data in 2021 - Expect initiation of dose expansion cohort in 2H2021


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Data from clinical database as of December 1, 2020 • Dose escalation progressing quickly with single-patient cohorts, >100-fold increase in 8 months • Once weekly administration tolerated, no DLTs observed to date Cohort Dose (µg) N 1 5 1 2 15 1 3 30 2 4 90 1 5 270 1 6 810 1 Total 7


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Data as of December 1, 2020 • HPN217 PK consistent with design and projection - Extended half-life: 104-225 hours over the dose range of 5 to 270µg/week - Dose proportional increase in Cmax and AUC - Dose independent clearance and volume of distribution, indicating linear kinetics [Graphic Appears Here] Nominal times used in analysis (instead of actual dosing time, similar results expected)


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Part 1 – Dose Escalation Dose Escalation: Single Patient Fixed Dosing ï,³ Gr 2 AE related or suspected related to HPN328 Dose Escalation: 3 + 3 (3 – 6 pts per cohort) Step dosing implemented at this point MTD or RP2D Part 2 – Dose Expansion Up to 27 patients with relapsed SCLC at the recommended phase 2 dose Simon 2-Stage Design • Target population - Small Cell Lung Cancer relapsed after platinum chemotherapy - Other malignancies with high grade neuroendocrine features R/R to Standard of Care (SOC) or no SOC available • Trial objectives - Assess safety and tolerability at increasing dose levels - pK and pharmacodynamic data - Evaluate preliminary anti-tumor activity • Dosing and administration - Weekly infusion of HPN328 starting at 15µg (flat dose) - Corresponds to EC50 - One cycle = 21 days (3 doses) - All patients: Premedication with dexamethasone, Tylenol, and histamine receptor blockers at initial dose(s) • Status - First site open and recruiting


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Data as of December 1, 2020 • HPN424: PSMA for prostate cancer – Clinical activity at 160ng/kg highest fixed dose tested (n=7) • 1 patient had confirmed RECIST partial response • Three of 7 (43%) had PSA reduction, one of which was a PSA50 – Patients now enrolling at 300 ng/kg in step-dose cohort • HPN536:    MSLN for ovarian, pancreatic and mesothelioma – Half-life extension of 70 hours supports once weekly HPN536 administration – 8 of 12 (67%) evaluable ovarian cancer patients showed stable target lesions – Patients now enrolling at 1200ng/kg in step-dose cohort • HPN217: BCMA for multiple myeloma – Dose escalation advancing to 6th dose cohort – >100 fold dose increase in 8 months – pK data confirms half-life extension • HPN328: DLL3 for small cell lung cancer and other neuroendocrine tumors – Designed for rapid escalation – Trial open for recruitment


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Broad Pipeline of Immuno-Oncology Programs Four Clinical Stage TriTAC Programs Product Stage of Development Anticipated 2021 Target / Indication Candidate Milestones Preclinical Phase 1 Phase 2 Phase 3 Data presentation 1H HPN424 PSMA / Prostate cancer Initiate expansion cohort 1H Dose expansion data EOY MSLN / Ovarian, Data presentation at a medical HPN536 pancreatic and other conference solid tumors Initiate expansion cohort 2H TriTAC Data presentation at a medical BCMA / Multiple HPN217 conference myeloma Initiate expansion cohort 2H DLL3 / Small cell lung Data presentation at a medical HPN328 cancer conference 2H IND-enabling studies Pro HPN601 EpCAM/GI cancers


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Spearheading Immunotherapies CLINICAL PIPELINE UPDATE DECEMBER 8, 2020