PVLA 8-K
Palvella Therapeutics, Inc. (PVLA)
8-K
2021-08-04
For: 2021-08-04
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April 10, 2026
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): August 4, 2021
(Exact name of registrant as specified in its charter)
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Registrant’s telephone number, including area code: 857 -246-8998
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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:
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Securities registered pursuant to Section 12(b) of the Act:
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (17 CFR §230.405) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR §240.12b-2).
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 2.02 Results of Operations and Financial Condition.
On August 4, 2021, Pieris Pharmaceuticals, Inc. (the “Company”) issued a press release announcing certain financial results for the quarter ended June 30, 2021. A copy of the press release issued by the Company is furnished as Exhibit 99.1 to this report.
The information set forth under this “Item 2.02. Results of Operations and Financial Condition,” including Exhibit 99.1 attached hereto, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, nor shall it be deemed incorporated by reference into any filing under the Securities Act of 1933, as amended, except as shall be expressly set forth by specific reference in such filing.
Item 7.01 Regulation FD Disclosure.
Attached hereto as Exhibit 99.2 and incorporated by reference herein is the August 2021 Investor Presentation of Pieris Pharmaceuticals, Inc.
The information set forth under this “Item 7.01. Regulation FD Disclosure,” including Exhibit 99.2 attached hereto, shall not be deemed “filed” for any purpose, and shall not be deemed incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended, regardless of any general incorporation language in any such filing except as shall be expressly set forth by specific reference in such filing.
Item 9.01 Financial Statements and Exhibits
(d) Exhibits.
SIGNATURE
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.
| PIERIS PHARMACEUTICALS, INC. | ||||||||
| Dated: August 4, 2021 | /s/ Tom Bures | |||||||
| Tom Bures | ||||||||
| Vice President, Finance | ||||||||
PRESS RELEASE PIERIS PHARMACEUTICALS REPORTS SECOND QUARTER 2021 FINANCIAL RESULTS AND PROVIDES CORPORATE UPDATE COMPANY TO HOST AN INVESTOR CONFERENCE CALL ON WEDNESDAY, AUGUST 4, 2021 AT 8:00 AM EDT • Announced inhaled program PRS-220 for the treatment of IPF and was selected to receive a Bavarian government grant of approximately $17 million to evaluate the program for post-COVID pulmonary fibrosis • Signed respiratory and ophthalmology agreement with Genentech with a $20 million upfront payment and more than $1.4 billion in potential additional milestone payments • Tim Demuth, M.D., Ph.D., appointed Chief Medical Officer and Shane Olwill, Ph.D., promoted to Chief Development Officer • Reiterated guidance for near-term and ongoing clinical studies • June 30th ending cash balance in excess of $119M BOSTON, MA, August 4, 2021 - Pieris Pharmaceuticals, Inc. (NASDAQ: PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin® technology platform for respiratory diseases, cancer, and other indications, today reported financial results for the second quarter of 2021 ended June 30, 2021 and provided an update on the Company’s recent and anticipated future developments. “We had a very productive second quarter, having advanced and expanded our pipeline while ending with a cash balance exceeding $119 million, largely bolstered by additional non-dilutive funding. As we further validate the Anticalin platform for local applications, we are pleased to have closed a strategic partnership with Genentech in the areas of respiratory and ophthalmology, providing another opportunity to grow our respiratory franchise while exploring a novel application for Anticalin proteins via ocular delivery. We are also excited to have unveiled our proprietary inhaled respiratory program PRS-220 for IPF alongside a grant from the Bavarian government to evaluate the program for post-COVID pulmonary fibrosis. PRS-220 is expected to enter the clinic next year. Additionally, we have made significant progress in advancing our immuno-oncology pipeline. In the coming weeks, we expect to dose the first patient in the phase 2 trial of cinrebafusp alfa in HER2-expressing cancers, for which FDA recently granted orphan drug designation, and we expect to start the phase 1 trial of PRS-344/S095012 with our partner, Servier, later this year,” said Stephen S. Yoder, President and Chief Executive Officer of Pieris. • PRS-060/AZD1402 and AstraZeneca Collaboration: Enrollment continues in the first (safety) part of the global phase 2a study of PRS-060/AZD1402, an inhaled IL-4 receptor alpha inhibitor under development in collaboration with AstraZeneca for the treatment of moderate-to-severe asthma. Pieris and AstraZeneca expect to announce data from the phase 2a study next year. Upon completion of the study, which is being sponsored and funded by AstraZeneca, Pieris will have the options to co-develop and, separately, co-commercialize PRS-060/AZD1402 in the United States. Pieris and AstraZeneca continue to advance each of the four programs in the collaboration beyond PRS-060/AZD1402. • Cinrebafusp Alfa (PRS-343): Pieris plans to dose the first patient in a two-arm phase 2 study for cinrebafusp alfa, a 4-1BB/HER2 bispecific for the treatment of HER2-expressing solid tumors, in gastric cancer in the coming weeks. One arm of the study will evaluate cinrebafusp alfa in combination with ramucirumab and paclitaxel in HER2-high gastric cancer, and the other arm of the study will evaluate cinrebafusp alfa in combination with tucatinib in HER2-low gastric cancer. As previously indicated, Go/No-Go criteria for advancement of this program will evaluate a composite
of measures, including a minimum target of 50% ORR in the HER2-high arm and a minimum target of 40% ORR in the HER2-low arm, duration of response, and safety. The Company expects to report results from both study arms next year. Recently, FDA granted orphan drug designation to cinrebafusp alfa for the treatment of HER2-high and HER2-low expressing gastric cancers. • PRS-344/S095012 and Servier Collaboration: The phase 1 study of PRS-344/S095012, a 4- 1BB/PD-L1 bispecific, is expected to begin later this year. Pieris holds exclusive commercialization rights for PRS-344/S095012 in the United States and will receive royalties on ex-U.S. sales for this program. Additionally, Servier has obtained in vivo proof of concept for PRS-352, an Anticalin-based bispecific beyond 4-1BB, triggering an undisclosed milestone payment to Pieris. Servier is responsible for further development of the program. • PRS-220: Pieris is developing PRS-220, a proprietary inhaled Anticalin protein targeting connective tissue growth factor (CTGF) for the treatment of idiopathic pulmonary fibrosis (IPF). The Company was selected to receive a 14.2 million euro (approximately 17 million USD) grant from the Bavarian government for the research and development of PRS-220 for post-acute sequelae of SARS-CoV- 2 infection (PASC) pulmonary fibrosis (PASC-PF), also known as post-COVID pulmonary fibrosis. The Company plans to present initial preclinical data from the program at the European Respiratory Society International Congress 2021 (ERS) in September, and clinical development is expected to begin next year. • Genentech Collaboration: Pieris entered into a multi-program research collaboration and license agreement with Genentech to discover, develop, and commercialize locally delivered respiratory and ophthalmology therapies that leverage Pieris’ proprietary Anticalin technology. Under the terms of the agreement, Pieris received a $20 million upfront payment, and may be eligible to receive more than $1.4 billion in additional milestone payments across multiple programs, including up to $11 million in preclinical milestones for each program, as well as tiered royalties up to low double- digits for any commercialized programs. The collaboration comprises two committed programs, and Genentech has an option to initiate up to two additional programs for a further payment of $10 million per program. • Executive R&D Leadership: Pieris announced the appointment of Tim Demuth, M.D., Ph.D. as SVP and Chief Medical Officer. Dr. Demuth will oversee all clinical, medical, safety, and regulatory aspects at the Company. Pieris additionally announced the promotion of Shane Olwill, Ph.D., to SVP and Chief Development Officer. In his new role, Dr. Olwill will lead all translational activities to inform the replenishing and positioning of Pieris’ portfolio across all stages of development in addition to overseeing project leadership on projects following declaration of a development candidate. First Quarter Financial Update: Cash Position – Cash and cash equivalents totaled $119.1 million for the quarter ended June 30, 2021, compared to a cash and cash equivalents balance of $70.4 million for the year ended December 31, 2020. The cash increase in the first half of 2021 was more than $78.0 million, primarily due to new and existing collaboration agreements, along with targeted use of the Company’s ATM program. This increase was partially offset by cash used to fund operations for the first six months of 2021. The June 30th cash position does not include the impact of the Bavarian government grant, as those proceeds will be reimbursed for qualifying program costs incurred over the PRS-220 development period. R&D Expense - R&D expenses were $15.8 million for the quarter ended June 30, 2021, compared to $11.3 million for the quarter ended June 30, 2020. The increase reflects higher spending on preclinical activities for PRS-220, an increase in manufacturing costs across multiple immuno-oncology programs, and higher royalty costs associated with entering new collaboration agreements.
G&A Expense - G&A expenses were $4.2 million for the quarter ended June 30, 2021, compared to $4.6 million for the quarter ended June 30, 2020. The decrease reflects lower legal and project management costs in 2021, along with higher one-time office and building equipment costs incurred related to the move to the new R&D facility in Hallbergmoos, Germany in the prior year. Net Loss - Net loss was $15.5 million or $(0.25) per share for the quarter ended June 30, 2021, compared to a net loss of $5.0 million or $(0.09) per share for the quarter ended June 30, 2020. Conference Call: Pieris management will host a conference call beginning at 8:00 AM EDT on Wednesday, August 4, 2021, to discuss the second quarter of 2021 financial results and provide a corporate update. Individuals can join the call by dialing +1-877-407-8920 (US & Canada) or +1-412-902-1010 (International). Alternatively, a listen-only audio webcast of the call can be accessed here. For those unable to participate in the conference call or listen to the webcast, a replay will be available on the Investors section of the Company's website, www.pieris.com. About Pieris Pharmaceuticals: Pieris is a clinical-stage biotechnology company that combines leading protein engineering capabilities and deep understanding into molecular drivers of disease to develop medicines that drive local biology to produce superior clinical outcomes for patients. Our pipeline includes inhalable Anticalin proteins to treat respiratory diseases and locally-activated bispecifics for immuno-oncology. Proprietary to Pieris, Anticalin proteins are a novel class of therapeutics validated in the clinic and by respiratory and immuno-oncology focused partnerships with leading pharmaceutical companies. For more information, visit www.pieris.com. Forward Looking Statements: This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, the potential for Pieris’ development programs such as PRS-060/AZD1402 and cinrebafusp alfa to address our core focus areas such as respiratory diseases and immuno-oncology, the advancement of our proprietary and co-development programs into and through the clinic and the expected timing for reporting data, making IND filings or achieving other milestones related to our programs, including PRS-060/AZD1402 and cinrebafusp alfa, the therapeutic potential of our Anticalin platform, our continued progress in the areas of co-stim bispecifics and inhaled therapeutics and the advancement of our developmental programs generally. Actual results could differ from those projected in any forward-looking statements due to numerous factors. Such factors include, among others, our ability to raise the additional funding we will need to continue to pursue our business and product development plans; the inherent uncertainties associated with developing new products or technologies and operating as a development stage company; our ability to develop, complete clinical trials for, obtain approvals for and commercialize any of our product candidates, including our ability to recruit and enroll patients in our studies; our ability to address the requests of the U.S. Food and Drug Administration; competition in the industry in which we operate; delays or disruptions due to COVID-19; and market conditions. These forward-looking statements are made as of the date of this press release, and we assume no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law. Investors should consult all of the information set forth herein and should also refer to the risk factor disclosure set forth in the reports and other documents we file with the Securities and Exchange Commission available at www.sec.gov, including without limitation the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2020 and the Company’s Quarterly Reports on Form 10-Q.
Investor Relations Contact: Pieris Pharmaceuticals, Inc. Maria Kelman Executive Director, Investor Relations +1 857 362 9635 [email protected]
PIERIS PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED BALANCE SHEETS (unaudited, in thousands) June 30, 2021 December 31, 2020 Assets: Cash and cash equivalents $ 119,097 $ 70,436 Accounts receivable 2,803 1,706 Prepaid expenses and other current assets 5,773 3,579 Total current assets 127,673 75,721 Property and equipment, net 20,373 22,046 Operating lease right-of-use assets 3,861 3,934 Other non-current assets 3,123 3,309 Total Assets $ 155,030 $ 105,010 Liabilities and stockholders’ equity: Accounts payable $ 2,310 $ 1,787 Accrued expenses 16,082 7,731 Deferred revenue, current portion 25,536 12,627 Total current liabilities 43,928 22,145 Deferred revenue, net of current portion 49,421 35,900 Operating lease liabilities 14,960 15,932 Other long-term liabilities — 6 Total Liabilities 108,309 73,983 Total stockholders’ equity 46,721 31,027 Total liabilities and stockholders’ equity $ 155,030 $ 105,010
PIERIS PHARMACEUTICALS, INC CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (unaudited, in thousands, except per share data) Three months ended June 30, Six months ended June 30, 2021 2020 2021 2020 Revenues $ 3,285 $ 11,246 $ 18,918 $ 24,507 Operating expenses Research and development 15,800 11,333 32,362 24,091 General and administrative 4,246 4,568 8,376 8,927 Total operating expenses 20,046 15,901 40,738 33,018 Loss from operations (16,761) (4,655) (21,820) (8,511) Interest income 3 129 6 448 Grant income 796 — 796 — Other income (expense), net 464 (424) 1,348 (484) Loss before income taxes (15,498) (4,950) (19,670) (8,547) Provision for income tax — — — — Net loss $ (15,498) $ (4,950) $ (19,670) $ (8,547) Basic and diluted net loss per share $ (0.25) $ (0.09) $ (0.33) $ (0.16) Basic and diluted weighted average shares outstanding 61,905 52,371 59,116 53,792
PIERIS PHARMACEUTICALS SUPERIOR MEDICINES THROUGH EFFICIENT BIOLOGY CORPORATE PRESENTATION August 2021
Forward-Looking Statements This presentation contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Statements in this presentation that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, the timing for initiation of clinical trials of PRS-220, whether PRS-220 will provide a clinical benefit in the treatment of IPF and PASC-related fibrosis, whether the combination of cinrebafusp alfa with other therapies could address a high medical need in HER2 gastric cancer patients who do not respond to traditional HER2-targeted therapies; whether the effects of the combination of cinrebafusp alfa with other therapies seen in preclinical studies will be observed in clinical trials; whether data from patients enrolled to date will be sufficient to inform the recommended phase 2 dose for the Company's planned proof of concept study of cinrebafusp alfa in gastric cancer; the expected timing and potential outcomes of the reporting by the Company of key clinical data from its programs, references to novel technologies and methods and our business and product development plans, including the Company's cash resources, the advancement of our proprietary and co-development programs into and through the clinic and the expected timing for reporting data, making IND filings or achieving other milestones related to our programs, including PRS- 060/AZD1402, cinrebafusp alfa, PRS-344, and PRS-352 and the expected timing of the initiation of the next stage of cinrebafusp alfa's development in gastric cancer. Actual results could differ from those projected in any forward-looking statements due to numerous factors. Such factors include, among others, our ability to raise the additional funding we will need to continue to pursue our business and product development plans; the inherent uncertainties associated with developing new products or technologies and operating as a development stage company; our ability to develop, complete clinical trials for, obtain approvals for and commercialize any of our product candidates, including our ability to recruit and enroll patients in our studies; our ability to address the requests of the U.S. Food and Drug Administration; competition in the industry in which we operate; delays or disruptions due to COVID-19; and market conditions. These forward-looking statements are made as of the date of this presentation, and we assume no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law. Investors should consult all of the information set forth herein and should also refer to the risk factor disclosure set forth in the reports and other documents we file with the Securities and Exchange Commission available at www.sec.gov, including without limitation the Company's Annual Report on Form 10-K for the fiscal year ended December 31, 2020 and the Company's Quarterly Reports on Form 10-Q. 2
Our Formula for Success 3 We combine leading protein engineering capabilities and deep insights into molecular drivers of disease to develop medicines that drive local biology to produce superior clinical outcomes for patients
Executive Summary 4 • Protein therapeutics that exploit biology validated by mAbs yet are engineered for focused activity at disease locus • Improved activity, reduced side effects, increased convenience Superior Medicines via Efficient Biology • Oral inhaled antagonists for respiratory disease • Locally activated immuno-oncology bispecifics • 2 POC readouts in '22; several follow-on candidates Two Focus Areas • ~$200M since 2017 in upfronts, milestones and equity investments • Several co-developed and out-licensed programs • Clinical supply for combination studies and development expertise Supportive Partnerships
A Novel Therapeutic Class with Favorable Drug-Like Properties • Human – Derived from lipocalins (human extracellular binding proteins) • Small – Monomeric, monovalent, small size (~18 kDa vs ~150kDa mAbs) • Stable – Inhalable delivery • Simple – Bi/multispecific constructs • Proprietary – Broad IP position on platform and derived products Translational Science Expertise to Deploy Platform in Meaningful Way • Immunology expertise underpins IO and respiratory focus • A leader in 4-1BB and costim biology • Patient phenotyping efforts for improved stratification and novel intervention points in, e.g., asthma Anticalin® Proteins as Therapeutic Modalities 5 Anticalin Protein Target
Two-fold Focus of Anticalin Platform Deployment Inhalable formulations to treat respiratory diseases locally 6 Bispecifics for local immune agonism to treat cancer Tumor cell Immune cell
Our Pipeline 7 IMMUNO-ONCOLOGY CANDIDATE TARGETS INDICATION PARTNER OUR COMMERCIAL RIGHTS DISCOVERY PRECLINICAL PHASE I PHASE II Cinrebafusp Alfa (PRS-343) 4-1BB/HER2 HER2-High GC** n/a Worldwide HER2-Low GC** PRS-344/S095012 4-1BB/PD-L1 n.d. US Rights; ex-US Royalties PRS-352 n.d. n.d. Royalties PRS-342/BOS-342 4-1BB/GPC3 n.d. Royalties Seagen Programs‡ Co-stim Agonist n.d. US Co-Promotion Option; Royalties ‡3 bispecific programs in collaboration with Seagen, with Pieris retaining a US co-promotion option for the second program ** Phase 2 study includes HER2-high arm in combination with ramucirumab and paclitaxel and HER2-low arm in combination with tucatinib; drug supply agreements with Lilly and Seagen, respectively RESPIRATORY CANDIDATE TARGETS INDICATION PARTNER OUR COMMERCIAL RIGHTS DISCOVERY PRECLINICAL PHASE I PHASE II PRS-060/AZD1402 IL4-Rα Asthma Worldwide Profit-Share Option PRS-220 CTGF IPF, PASC-PF n/a Worldwide AstraZeneca Programs* n.d. n.d. Worldwide Profit-Share Options Genentech Programs+ n.d. n.d. Royalties *4 respiratory programs in collaboration with AstraZeneca, 2 of which carry co-development and co-commercialization options for Pieris +Collaboration includes 1 respiratory program and 1 ophthalmology program 7
Validating Partnerships with Leading Companies • PRS-060/AZD1402 + 4 additional programs • Upfront & milestones to date: $70.5M • $10M equity investment from AstraZeneca • Eligible to receive up to approximately $5.4B in potential milestone payments plus royalties • Retained co-development and co- commercialization (US) options on PRS-060 and up to 2 additional programs • Boston Pharmaceuticals holds exclusive license for PRS-342/BOS-342 • Upfront & milestones to date: $10M • Eligible to receive up to approximately $353M in potential milestone payments • Entitled to tiered royalties • 1 respiratory program + 1 ophthalmology program • Upfront & milestones to date: $20M • Eligible to receive over $1.4B million in potential milestone payments • Entitled to tiered royalties • Genentech has option to select additional targets in return for an option exercise fee • 3-program IO bispecific partnership • Upfront & milestones to date: $35M • Eligible to receive up to approximately $1.2B in potential milestone payments plus royalties • $13M equity investment from Seagen • Tucatinib drug supply for phase 2 combination trial of cinrebafusp alfa in HER2-low gastric cancer • PRS-344/S095012: PD-L1/4-1BB antibody- Anticalin bispecific, for which Pieris holds full U.S. rights • Upfront & milestones to date: ~$40M • Eligible to receive up to approximately $447M in potential milestone payments • Entitled to tiered royalties 8
Anticalin Technology Advantages: Differentiated Respiratory Platform 9 • Lipocalin templates deployed by Pieris in respiratory programs are abundant in the human lung and can permeate lung epithelium • Stable, monovalent molecules with high melting temperatures and insensitivity to mechanical stress • Inhalation pharmacokinetics suitable for once or twice daily administration and compatible with flexible treatment regimens • Control of particle size distribution in critical size range in both “wet” and “dry” formulations to enable tailored delivery to discrete lung regions
PRS-060/AZD1402: Inhaled IL-4Rα Antagonist 10 PRS-060/AZD1402Candidate Inhibiting IL4-Rα (disrupts IL-4 & IL-13 signaling)Function/MoA Moderate-to-severe asthmaIndications Phase 2a in moderate asthmaticsDevelopment Co-development and U.S. co-commercialization options, including gross margin shareCommercial Rights PRS-060/AZD1402
PRS-060 Phase 2a Trial 11 Patient Population: Moderate controlled asthmatics Primary Endpoint: Safety and tolerability Number of Patients: ~45 Part 1 Patient Population: Moderate uncontrolled asthmatics with blood eosinophil count of ≥ 150 cells/μL and FeNO ≥ 25 ppb at screening Primary Endpoint: Improvement of FEV1 over four weeks relative to placebo Number of Patients: ~360 Part 2 Study is sponsored and funded by AstraZeneca Enrollment initiated 1Q 2021 Dry powder formulation, administered b.i.d. over four weeks Up to three dose levels plus placebo
PRS-220: Inhaled CTGF Antagonist 12 PRS-220Candidate Inhibiting CTGF/CCN2Function/MoA IPF and PASC-PF*Indications Entering phase 1 in 2022Development Fully proprietaryCommercial Rights PRS-220 *Idiopathic Pulmonary Fibrosis and Post-Acute sequelae of SARS-CoV-2 infection (PASC) Pulmonary Fibrosis
IPF: High Unmet Medical Need and Significant Commercial Opportunity people affected worldwide with increasing global incidence, with ~130K affected in the US each year1,2 3 to 5 million mean survival from the time of diagnosis2 2 to 5 years current market in sales>$3B 13 1 – Glassberg, AJMC 2019 2 - Meltzer, Orphanet Journal of Rare Diseases 2008 Martinez, Nature Rev Dis Primer, 2017 IPF is a chronic, progressive, and ultimately fatal lung disease of unknown cause characterized by chronic lung inflammation and progressive scarring (fibrosis) of the tissues between the alveoli of the lung Currently approved treatments provide modest benefit, in addition to having side effects that require management
CTGF: Clinically Validated Intervention for IPF • Connective tissue growth factor (CTGF), or CCN2, a protein localized in the extracellular matrix, is a driver of fibrotic remodeling as consequence of an aberrant wound healing process • Over-expression of the protein in lung tissue is observed in patients suffering from IPF • Competitor clinical data indicate inhibition of CTGF reduces the decline in lung function among patients with IPF • Competitor compound requires high- dose infusions to effectively target lung- resident CTGF 14 (Lipson, Fibrogenesis & Tissue Repair, 2012) CTGF affects multiple signaling pathways and processes important in pathophysiology. CTGF interacts with a variety of molecules, including cytokines and growth factors, receptors and matrix proteins. These interactions alter signal transduction pathways, either positively or negatively, which results in changes in cellular responses.
PRS-220: Inhaled Solution The only CTGF inhibitor in clinical trials for IPF is a monoclonal antibody administered by IV infusion, 30 mg/kg every three weeks The objective of PRS-220 is to more efficiently engage a clinically validated target via oral inhalation directly to the lung epithelium and interstitium Benefits of inhaled administration: • Inhaled administration eliminates the need for additional clinic visits required for systemic drug administration • Direct administration into the lungs may result in more efficient CTGF inhibition in the site of the disease • Patients with IPF frequently take inhaled medications and thus no additional training required • This approach supports add-on to SOC, whereas patients on SOC are excluded from current studies of reference mAb 15
Grant From Bavarian Government to Support Program Acceleration and Evaluation of Efficacy in PASC-PF approximately 14 million euro grant from the Bavarian government for the research and development of PRS-220 for post-acute sequelae of SARS-CoV-2 infection (PASC) pulmonary fibrosis (PASC-PF) 16 ~$17M • Allow Pieris to accelerate development of the program – IND planned 2022 • Support clinical-readiness activities and initial clinical development for the program, including GLP tox studies, GMP manufacturing, and phase 1 clinical development • Broaden scope of the program beyond the original IPF indication by including the evaluation of PRS-220 for the treatment of post-COVID-19-related pulmonary fibrosis Grant will:
PRS-220 for PASC-PF 17 Post-acute sequelae of SARS-CoV-2 infection (PASC) pulmonary fibrosis (PASC-PF), also known as post-COVID-19 syndrome pulmonary fibrosis, affects patients who have recovered from acute COVID-19 Blocking CTGF with an inhaled Anticalin protein may reduce the extent and persistence of fibrotic interstitial lung disease in patients after moderate and severe COVID-19 CTGF About a third of patients hospitalized with severe COVID-19 have persistent interstitial lung abnormalities lasting up to six months after infection Prevalence PASC-PF
Cinrebafusp Alfa (PRS-343): Lead IO Asset 18 Cinrebafusp alfa (PRS-343)Candidate Tumor-targeted 4-1BB agonism and HER2 antagonismFunction/MoA HER2-high and HER2-low gastric cancerIndications Initiating phase 2Development Fully proprietaryCommercial Rights HER2-Targeting Antibody 4-1BB-Targeting Anticalin Proteins
Cinrebafusp Alfa Phase I Summary • Acceptable profile observed at all doses tested with no dose-limiting toxicities • Clinical benefit at active dose levels (≥2.5 mg/kg), including confirmed complete response and several confirmed partial responses • Dose-dependent immune activation and 4-1BB modulation in both HER2-high and HER2-low expressing patients • Durable anti-tumor activity in heavily pre-treated patient population, including "cold" tumors • Moving into phase 2 in HER2-high and HER2-low gastric cancer • As lead IO program, cinrebafusp alfa provides key validation of 4-1BB franchise and follow-on programs, including PRS-344 and PRS-342 19
Cinrebafusp Alfa Phase 1 Monotherapy Study 20 Study Objectives Primary: Characterize Safety Profile Identify MTD or RP2D Secondary: Characterize PK/PD & Immunogenicity Preliminary anti-tumor activity Key Eligibility Criteria Inclusion: Metastatic HER2+ solid tumors Breast & Gastric/GEJ ≥ 1 prior anti-HER2 Tx Measurable disease (RECIST v1.1) ECOG 0 or 1 Exclusion: Symptomatic or unstable brain metastasis Abnormal cardiac EF (< 45%) 0.0005 mg/kg 0.05 mg/kg 0.15 mg/kg (n = 5) 0.5 mg/kg (n = 7) 1.0 mg/kg (n = 6) 2.5 mg/kg (n = 6) 5 mg/kg (n = 9) 8 mg/kg (n = 26) 12 mg/kg (n = 3) 18 mg/kg (n = 9) (n = 7) Accelerated Titration Dose Escalation Study Design Q3W Q2W QW, Q2W & Q3W active dose range 13b 12b 11, 11b, 11c, obi 10 9 8 7 6 5
Phase 1 Monotherapy Treatment Related Adverse Events at Active Doses (≥ 2.5 mg/kg) 21 Data cut-off: 25-Feb-21 Treatment Related Adverse Events (TRAEs occurring in > 1 patient; n = 53) All Grades n (%) Grade 1-2 n (%) Grade 3-4 n (%) Infusion related reaction 13 (25%) 9 (17%) 4 (8%) Nausea 7 (13%) 7 (13%) Chills 6 (11%) 6 (11%) Vomiting 6 (11%) 6 (11%) Dyspnea 4 (8%) 4 (8%) Fatigue 4 (8%) 4 (8%) Arthralgia 3 (6%) 2 (4%) 1 (2%) Decreased appetite 3 (6%) 3 (6%) Non-cardiac chest pain 3 (6%) 3 (6%) Asthenia 2 (4%) 2 (4%) Diarrhea 2 (4%) 2 (4%) Dizziness 2 (4%) 2 (4%) Headache 2 (4%) 2 (4%) Paresthesia 2 (4%) 1 (2%) 1 (2%) Pruritus 2 (4%) 2 (4%) Pyrexia 2 (4%) 2 (4%) Rash 2 (4%) 2 (4%) 1 Gr 3 Ejection Fraction dec and 1 Gr 3 Heart Failure; both events occurred in one patient and resolved w/o sequelae.
Summary of Responses in Phase 1 Monotherapy Study 22 Cohort 13b 12b 11c Obi 11b 11 10 9 Total Best Response 18 mg/kg, Q2W 12 mg/kg, Q2W 8 mg/kg, QW 8 mg/Kg, Q2W 8 mg/kg, Q2W 8 mg/kg, Q3W 5 mg/kg, Q3W 2.5 mg/kg, Q3W Evaluable Patients 8 2 5 4 7 4 7 5 42 CR 1 - - - - - - - 1 PR 1 - - - 3 - - - 4 SD 3 - 1 2 3 3 3 2 17 ORR 25% 0% 0% 0% 43% 0% 0% 0% 12% DCR 63% 0% 20% 50% 86% 75% 43% 40% 52% Data cut-off: 25-Feb-21
Cinrebafusp Alfa Phase 1 Monotherapy Efficacy Data: Analysis of Patients Treated at Active Doses 23 Overall Population Data cut-off: 25-Feb-21 *Manual update for CUP patient from Medidata 9-Apr-21 *
Durable Responses with Cinrebafusp Alfa Among Heavily Pre-treated Population 24 Data cut-off: 25-Feb-21 Overall Population
Cinrebafusp Alfa Shows Dose-dependent Activity Across Key Pharmacodynamic Parameters 25 Se ru m (s 4- 1B B ) Tu m or (C D 8+ ) Mann-Whitney U TestConnects group averages Dose at 8 mg/kg incorporates patients treated at Q1W, Q2W, or Q3W Median Data cut-off: 25-Feb-21
Cinrebafusp Alfa Activates Adaptive and Innate Immunity in the Tumor 26 Data cut-off: 25-Feb-21 p = 0.002 CD8+ Cells p = 0.0115 CD8+Ki67+ Cells p = 0.0051 NK Cells p = 0.1551 GrzB+ Cells Denotes group averages Median Unpaired One-Tailed Welch`s Biopsy Pre-dose Biopsy Post-dose (Cycle 2 Days 2-8) PRS-343 (Cycle 2 Day 1) PRS-343 (Cycle 1 Day 1) p=0.0782 Based on preclinical and clinical data, serum concentration of > 20 µg/ml defines active dose range beginning at 2.5 mg/kg (Cohort 9)
Single-Agent Activity in Both “Hot” and “Cold” Tumors 27 Data cut-off: 25-Feb-21 PD-L1 status and CD8+ T cells levels in tumor biopsies Several patients with clinical benefit have low/negative PD-L1 status and low CD8 T cell numbers PR SD CR * Threshold informed by (Tumeh et al., 2014 and Blando et al., 2019) Cold Tumor Hot Tumor & PD-L1 High CD8 High/PD-L1 Low/Negative CD8 Low/PD-L1 High *
Signs of Preclinical and Clinical Activity in the HER2-Low Setting 28 PRS-343 increases soluble 4-1BB in HER2-low-expressing patients Baseline On-tx 0 5 10 40 60 Her 2 IHC 2+ Her 2 IHC 1+ PRS-343 enhances T cell activation in in vitro co-cultures with HER2-low tumor cell lines1 1Hinner et al Clin Can Res 2019 Her 2 IHC 2+ Her 2 IHC 1+ Patient with SD Patient with PD Fo ld c ha ng e IL 2 (L og 2) Normalized HER2 expression JIMT-1 MDA-MB-453 ZR-75-1 MKN7 MKN45 Data cut-off: 25-Feb-21
Cinrebafusp Alfa Clinical Development Plan 29 Go/No-Go Analysis Gastric Cancer 2L+ AR M A HER2-High (IHC3+ or IHC2+/ISH+) Cinrebafusp Alfa + Ramucirumab + Paclitaxel Phase 2 Details add. 20 – 40 pts add. 20 – 40 pts and Part BPart A N = ~ 20 pts N = ~ 20 pts Gastric Cancer 2L+ AR M B HER2-Low (IHC2+/ISH- or IHC1+) Cinrebafusp Alfa + Tucatinib Recommended Phase 2 Dose: Two-cycle loading dose of 18 mg/kg (Q2W), followed by an 8 mg/kg dose (Q2W) in subsequent cycles High bar based on ORR, durability, and safety
Cinrebafusp Alfa Opportunity in HER2-High & HER2-Low Gastric Cancer 30 1st Line 2nd Line 3rd Line Cinrebafusp Alfa Initial Focus *HER2-Low = IHC2+/ISH- or IHC1+ US Incidence: ~800 EU5 Incidence: ~1,300 JP Incidence: ~3,500 US Incidence: ~1,500 EU5 Incidence: ~2,800 JP Incidence: ~5,000 US Incidence: ~2,600 EU5 Incidence: ~5,200 JP Incidence: ~9,500 US Incidence: ~3,700 EU5 Incidence: ~7,400 JP Incidence: ~13,400 US Incidence: ~2,100 EU5 Incidence: ~4,000 JP Incidence: ~7,000 US Incidence: ~1,100 EU5 Incidence: ~1,700 JP Incidence: ~4,900 1) Meta Analysis of 12 studies (10,287 patients; Range 12.3-26.9%) 2) Eric Van Cutsem, et al., Gastric Cancer (2015) 18:476–484 ~17%1 HER2-high Patients ~24%2 HER2-low* Patients Total US, EU5 & JP Incidence (HER2+ & HER2-Low): ~35,000
PRS-344/S095012: Meaningfully Building on Localized MoA of Cinrebafusp Alfa 31 PRS-344/S095012Candidate Localized 4-1BB agonism with PD-L1 antagonismFunction/MoA N.D.Indications 2021 IND expected (in co-dev with Servier)Development Co-development with full U.S. commercial rights; royalty on ex-U.S. salesCommercial Rights PD-L1-Targeting Antibody 4-1BB-Targeting Anticalin Proteins
PRS-344 Drives Strong Anti-tumor Activity in Anti-PD-L1 mAb- resistant Mouse Model 33 • Dose-dependent anti-tumor response that leads to significant extension of survival • Superior to equimolar doses of anti-PD-L1 mAb treatment alone h-4-1BB knock-in mice subcutaneously implanted with MC-38-huPD-L1 cells Tumor Growth Survival 0 10 20 30 40 50 0 20 40 60 80 100 0 5 10 15 20 25 30 35 0 1000 2000 3000 4000 *** ****** *** * ** * PRS-344/S095012 (1 mg/kg) anti-4mAb 3mg/kg Vehicle control PRS-344/S095012 (10 mg/kg) PRS-344/S095012 (0.01 mg/kg) anti-PD-L1 mAb (7.7 mg/kg) anti-PD-L1 mAb (0.8 mg/kg) PRS-344/S095012 (0.1 mg/kg) Days after implantationDays after implantation Vehicle Anti-PD-L1 - 7.7 mg/kg Anti-PD-L1 – 0.77 mg/kg Urelumab analog – 3 mg/ PRS-344/S095012 - 10 mg/kg PRS-344/S095012 - 1 mg/kg PRS-344/S095012 - 0.1 mg/kg PRS-344/S095012 - 0.01 mg/kg
Financial Overview (As of 6/30/21) 34 non-dilutive capital from partnerships since 2017>$175M $119.1M Cash & Cash Equivalents $0.0 Debt 66.7M CSO grant announced in 2021>$17M>$17M
Appendix
PRS-060 Phase I
PRS-060 Phase I Multiple Ascending Dose Trial Ascertain PK/PD with a reliable biomarker to confirm local target engagement and inform Phase II dosage regimenStrategic Objectives Dosing patients with mild asthma with elevated FeNO levels (≥35 ppb), to receive inhaled PRS-060 or pbo b.i.d.* over a 10-day periodTrial Design Highlights Pieris is sponsoring the trial, AstraZeneca is reimbursing Pieris for all associated costs Initiated in July 2018 Evaluating safety, tolerability, PK, PD and will also evaluate FeNO reduction vs. placebo Measuring safety, tolerability and FeNO changes days 1-10,17, and 40 *q.d. on Day 10 37
Phase 1b Interim Results: Favorable Safety Profile 38 • All doses of AZD1402/PRS-060 tested in the study were well tolerated • No treatment-related serious AEs were observed System organ class AE Preferred Termsb Placebo (N = 12) n (%) m AZD1402/PRS-060c (N = 30) n (%) m Overall (N = 42) n (%) m Gastrointestinal disorders Dry mouth Nausea 4 (33.3) 4 1 (8.3) 1 1 (8.3) 1 13 (43.4) 14 2 (6.7) 2 3 (10.0) 3 17 (40.5) 18 3 (7.1) 3 4 (9.5) 4 Infections and infestations Upper respiratory tract infection 1 (8.3) 1 1 (8.3) 1 7 (23.3) 8 3 (10.0) 4 8 (19.0) 9 4 (9.5) 5 Nervous system disorders Headache Presyncope 5 (41.7) 9 3 (25.0) 6 0 13 (43.4) 18 5 (16.7) 7 4 (13.3) 6 18 (42.9) 27 8 (19.0) 13 4 (9.5) 6 Respiratory, thoracic and mediastinal disorders Cough Rhinorrhoea Wheezing 6 (50.0) 6 1 (8.3) 1 2 (16.7) 2 2 (16.7) 2 14 (46.7) 15 4 (13.3) 4 1 (3.3) 1 4 (13.3) 5 20 (47.6) 21 5 (11.9) 5 3 (7.1) 3 6 (14.3) 7
Phase 1b Interim Results: Robust FeNO Reduction 39 PRS-060 Relative FeNO Reduction (Emax Analysis) PRS-060, mg (delivered) n Reduction vs. placebo, % (95% CI) p-value 2 6 24.0 (1.8–41) 0.04 6 6 24.3 (2.7–41) 0.03 20 12 36.4 (22–48) <0.0001 60 6 30.5 (10–46) 0.005 Placebo 12 PRS-060 Relative FeNO Reduction (ANCOVA Analysis) Mean change from baseline in FeNO levels at 0.5h (A) and 2h (B) post-dose on Day 10 in participants with mild asthma
Phase 1b Interim Results: Pharmacological Versatility 40 pSTAT6 levels over time following inhalation of PRS-060 No systemic target engagement and minimal systemic exposure was observed at the 2mg dose, suggesting that local target engagement by the drug is sufficient to reduce airway inflammation Pharmacological versatility, given low- dose FeNO reduction with no observed systemic activity (pSTAT6) versus high-dose FeNO reduction with systemic activity
Cinrebafusp Alfa – Phase I Monotherapy
Phase 1 Monotherapy Baseline Characteristics (N = 78) 42 Characteristic n (%) Age, Median (range) 63 (24–92) Gender F 46 (59%) M 32 (41%) ECOG PS 0 19 (24%) 1 59 (76%) Prior Therapy Lines 1 11 (14%) 2 10 (13%) 3 16 (21%) 4 12 (15%) 5+ 29 (37%) Median # of anti-HER2 Tx Breast 6 Gastric 2 Primary Cancer Type n (%) Gastroesophageal 34 (44%) Breast 16 (21%) Colorectal 12 (15%) Gynecological 9 (12%) Bladder 2 (3%) Pancreatic 1 (1%) Other – Cancer of Unknown Origin 2 (3%) Other – Salivary Duct 1 (1%) Melanoma 1 (1%) Data cut-off: 25-Feb-21
Cinrebafusp Alfa Phase 1 Monotherapy Efficacy Data: Analysis of Patients Treated at Active Doses 43 GC/GEJ & Colorectal Cancers Data cut-off: 25-Feb-21
Case Studies: PR in Gastric Cancer and CR in Rectal Cancer Patient Profile, Treatment History and Treatment Outcome 44 Rectal Cancer Patient with Complete Response • 59-year-old male; initial diagnosis in March 2017 • Rectal cancer with cardiac and lung mets • Treated with 18 mg/kg Q2W of PRS-343 • Foundation One Her2 amplification; verified in-house to be IHC 3+; MSS, TMB low Prior Treatment includes: • Folfiri/Avastin • 5FU/Avastin maintenance • Irinotecan/Avastin & SBRT Gastric Cancer Patient with Partial Response • 80-year-old woman; initial diagnosis in June 2017 • Gastric adenoca with mets to liver, LN and adrenals • Treated with 8 mg/kg Q2W of PRS-343 • HER2 IHC 3+; PD-L1 positive (CPS=3) ; NGS: ERBB2 amplification Prior Treatment includes: • Trastuzumab, Pembrolizumab + Capecitabine/oxaliplatin • Nivolumab with IDO1 inhibitor (investigational drug) Pre C D 8 + T ce lls (n /m m 2 ) 0 100 200 300 400 500 600 700 Post CD8 fold change: 2.3 CD8 pre [n/mm2]: 238 2 3 4 8 1 5 0 2 4 6 s 4 1 B B F o ld C h a n g e t o B a s e li n e T i m e p o i n t ( d a y s ) B a s e l i n e P r e C 2 Pre C D 8 + T ce lls (n /m m 2 ) Post CD8 fold change: 5.7 CD8 pre [n/mm2]: 38 0 50 100 150 200 250 B as el in e C 4 Po st -tr ea tm en t B as el in e C 6 Po st -tr ea tm en t 2 4 8 15 Pre C2 0 1 2 3 s4 1B B Fo ld C ha ng e to P re do se Timepoint (days) Baseline
Case Study: PR in Cancer of Unknown Primary Patient Profile, Treatment History and Treatment Outcome 45 Data cut-of: 25-Feb-21 Lesions Lesion Site Lesion Size (mm) Pre-treatment Post-treatment Cycle 2 Cycle 4 Cycle 6 Target 1 Lung, right lower lobe mass 25 13 0 0 Total 25 13 0 0 % Change from Baseline -48% -100% -100% Non-target 1 Lung, bilateral pulmonary masses Present Not assessed Present Present Non-target 2 Lymph nodes, mediastinal and hilar Present Not assessed Present Present Overall Response PR PR PR Patient Profile 82-year-old male Initial diagnosis October 2019 Carcinoma of Unknown Primary Stage 4 HER2 amplification via MD Anderson NGS; MSS- stable; TMB unknown Treatment History Open Radical Prostatectomy Radiation Carboplatin + gemcitabine Bas eli ne C1 d 2 C1 d 3 C1 d 4 C1 d 8 C1 d15 Pre C2 Pre C3 C3 d 2 C3 d 3 C3 d 4 C3 d 8 C3 1 5 0 5 10 15 Timepoint (days) Fo ld c ha ng e to b as el in e s4 -1 B B S er um Data cut-off: 25-Feb-21
Case Study: SD in Colorectal Cancer Patient Profile, Treatment History and Treatment Outcome 46 Lesions Lesion Site Lesion Size (mm) Pre-treatment Post-treatment Cycle 2 Cycle 4 Cycle 6* Target 1 Lung, right upper lobe pulmonary nodule 10 8 8 - Target 2 Lung, right lower lobe pulmonary nodule 12 11 11 - Total 22 19 19 - % Change from Baseline -14% -14% - Non-target 1 Lung, multiple pulmonary nodules Present Present Present - CEA <1.9 1.1 1.3 - Patient Profile 56-year-old female Initial diagnosis Jan 2009 Stage 4 Colorectal Adenocarcinoma Cancer Archival HER2 3+ MSI stable; KRAS, NRAS, BRAF wt Treatment History 9 prior lines of therapy, including: Folfiri Folfox + Avastin 5-FU + bevacizumab trastuzumab/pertuzumab Investigational agent (immune stimulator antibody conjugate (ISAC) with antibody similar to trastuzumab s4 -1 B B S er um Bas eli ne C1 d 2 C1 d 3 C1 d 4 C1 d 8 C1 d 15 Pre C2 Pre C3 C3 d 2 C3 d 3 C3 d 4 C3 d 8 C3 1 5 0 5 10 15 Timepoint (days) Fo ld c ha ng e to b as el in e Data cut-off: 25-Feb-21 *Data not yet available due to COVID-related delays
Cinrebafusp Alfa – Biomarkers
Soluble 4-1BB (s4-1BB): Blood-based Biomarker of Cinrebafusp Alfa Engagement 48 • s4-1BB is an alternatively spliced form of 4-1BB receptor lacking the transmembrane encoding exon (Setareh et al., 1995; Shao et al., 2008) • s4-1BB is released by leukocytes in an activation-dependent manner (Michel et al., 2000; Salih et al., 2001; Schwarz et al., 1996) • s4-1BB is produced with a slightly delayed kinetic to pathway activation. Hypothesized role is as a negative regulator, keeping 4-1BB-mediated co-stimulation in check s4-1BB utility as a pathway specific biomarker provides ability to track cinrebafusp target engagement and activity using serum samples
Cinrebafusp Alfa – Phase II Rationale
Scientific Rationale for Combining Cinrebafusp Alfa & SoC 50 • Reduces tumor bulk • Releases antigen • Improves T cell : tumor target ratio Paclitaxel – Chemotherapy • Normalizes vascularization • Alters tumor barrier to T cell penetration • Reduces Tregs & inhibits TAMs Ramucirumab – Anti-Angiogenic1-3 • Increases T cell survival and metabolic fitness in the TME • Induces T cell memory • Drives T cell expansion • Induces anti-tumor cytolytic activity Cinrebafusp Alfa – 4-1BB Agonist 1 - Allen et al., Science Translational Medicine 2017 2 - Juang et al. Front Immunology 2018 3 - Tada et al., Journal for Immunotherapy of Cancer 2018
Scientific Rationale for Combining Cinrebafusp Alfa & Tucatinib 51 • Upregulates or stabilizes tumor cell surface HER2 expression2,3,4 • Increases clustering potential of cinrebafusp alfa on tumor cells to drive enhanced 4-1BB cross-linking Tyrosine kinase inhibitors (tucatinib) • Inhibits HER2 signaling AND activates tumor-specific T cells in tumor microenvironment Cinrebafusp Alfa – Dual MoA • Enhances inhibition of HER2 signaling by concurrent binding to HER2 on the tumor cell surface and TKI inhibition of the internal kinase signaling domain1 • In vitro, combination leads to significantly increased T cell activation in the presence of HER2-Low cell lines Complements Both MoAs 1 - Baselga J., Lancet, 2012; 2 - Maruyama T., et al, Anticancer Res., 2011 3 - Scaltriti M., et al, Oncogene, 2009 4 - Hartmans, et al, Oncotarget,, 2017
Cinrebafusp Alfa and Tucatinib Combination Enhances T-cell Activation 52 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0 50 100 150 200 #19074 | MKN-7 Concentration [nM] IL -2 [p g/ m l] bg12 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0 100 200 300 #19074 | HT-29 Concentration [nM] IL -2 [p g/ m l] bg1bg2 PRS-343 PRS-343 + tucatinib Tras-IgG4 Tras-IgG4 + tucatinib urelumab urelumab + tucatinib 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0 1000 2000 3000 #19074 | SK-BR-3 Concentration [nM] IL -2 [p g/ m l] bg1 bg2 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0. 00 04 2 0. 00 13 0. 00 38 0. 01 1 0. 03 4 0. 10 0. 31 0. 93 2. 8 8. 3 25 0 50 100 150 200 250 #19074 | ZR-75-1 Concentration [nM] IL -2 [p g/ m l] bg12 PRS-343 PRS-343 + tucatinib Tras-IgG4 Tras-IgG4 + tucatinib urelumab urelumab + tucatinib Increased IL-2 secretion observed when cinrebafusp alfa was combined with fixed dose tucatinib in a co-culture assay with SK-BR-3 (high HER2), MKN-7, ZR-75-1 (medium HER2) and HT-29 (low HER2) tumor cell lines SK-BR-3 (HER2+++) MKN-7 (HER2++) HT-29 (HER2+) ZR-75-1 (HER2++) Human T cell Co-Culture Activation Assay
Cinrebafusp Alfa and Tucatinib Combination Leads to Enhanced 4-1BB Signaling 53 PRS-343 PRS-343 + tucatinib Tras-IgG4 Tras-IgG4 + tucatinib urelumab urelumab + tucatinibPRS-343 PRS-343 + tucatinib Tras-IgG4 Tras-IgG4 + tucatinib urelumab urelumab + tucatinib Increased 4-1BB signaling observed when cinrebafusp alfa was combined with fixed dose tucatinib in a reporter assay with SK-BR-3 (high HER2), MKN-7, ZR-75-1 (medium HER2) and HT-29 (low HER2) tumor cell lines 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0 200000 400000 600000 800000 Concentration [nM] R LU bg1 bg2 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0 200000 400000 600000 800000 Concentration [nM] R LU bg1 bg2 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0 200000 400000 600000 800000 Concentration [nM] R LU bg1 bg2 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0. 00 1 0. 00 4 0. 01 1 0. 03 4 0. 10 3 0. 30 9 0. 92 6 2. 77 8 8. 33 3 25 0 50000 100000 150000 200000 600000 800000 1000000 Concentration [nM] R LU bg1 bg2 SK-BR-3 (HER2+++) MKN-7 (HER2++) HT-29 (HER2+) ZR-75-1 (HER2++) (4-1BB Reporter Cell Assay)
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