Merus Announces First Patient Dosed in LiGeR-HN2, a Phase 3 Trial Evaluating Petosemtamab in 2/3L r/m HNSCC

On July 24, 2024 Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported that the first patient has been dosed in the Company’s phase 3 trial evaluating the efficacy and safety of petosemtamab, a Biclonics targeting EGFR and LGR5, compared to investigator’s choice of single agent chemotherapy or cetuximab in previously treated (2/3L) patients with recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC) referred to as the LiGeR-HN2 trial (Press release, Merus, JUL 24, 2024, View Source [SID1234645067]).

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Merus has confirmed through feedback with the U.S. Food and Drug Administration (FDA) that petosemtamab 1500 mg every two weeks is appropriate for further development in HNSCC as monotherapy, and in combination with pembrolizumab.

"With petosemtamab’s strong clinical data in HNSCC and alignment with the FDA on dose, we are excited to have treated our first patient in the 2/3L phase 3 trial," said Fabian Zohren, M.D., Ph.D., Chief Medical Officer of Merus. "We believe petosemtamab has the potential to become the new standard of care across r/m HNSCC."

More details of the trial can be found at clinicaltrials.gov.

About LiGeR-HN2
LiGeR-HN2, a phase 3 trial, will evaluate the safety and efficacy of petosemtamab compared to investigator’s choice of methotrexate, docetaxel, or cetuximab in 2/3L r/m HNSCC patients. The trial is open to adult patients that have progressed on or after anti-PD-1 therapy and platinum-containing therapy. The primary endpoints are overall response rate as assessed by BICR based on RECIST v1.1 and overall survival. Secondary endpoints are duration of response and progression free survival. Merus plans to enroll approximately 500 patients in the trial.

About Petosemtamab
Petosemtamab, or MCLA-158, is a Biclonics low-fucose human full-length IgG1 antibody targeting the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5). Petosemtamab is designed to exhibit three independent mechanisms of action including inhibition of EGFR-dependent signaling, LGR5 binding leading to EGFR internalization and degradation in cancer cells, and enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activity.

About Head and Neck Cancer
Head and neck squamous cell carcinoma (HNSCC) describes a group of cancers that develop in the squamous cells that line the mucosal surfaces of the mouth, throat, and larynx. These cancers begin when healthy cells change and grow in an unchecked manner, ultimately forming tumors. HNSCC is generally associated with tobacco consumption, alcohol use and/or HPV infections, depending on where they develop geographically. HNSCC is the sixth most common cancer worldwide and it is estimated that there were more than 930,000 new cases and over 465,000 deaths from HNSCC globally in 2020.1 The incidence of HNSCC continues to rise and is anticipated to increase by 30% to more than 1 million new cases annually by 2030.2 HNSCC is a serious and life-threatening disease with poor prognosis despite currently available standard of care therapies.

Thermo Fisher Scientific Reports Second Quarter 2024 Results

On July 24, 2024 Thermo Fisher Scientific Inc. (NYSE: TMO), the world leader in serving science, reported its financial results for the second quarter ended June 29, 2024 (Press release, Thermo Fisher Scientific, JUL 24, 2024, View Source [SID1234645045]).

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Second Quarter 2024 Highlights

•Second quarter revenue was $10.54 billion.
•Second quarter GAAP diluted earnings per share (EPS) increased 15% to $4.04.
•Second quarter adjusted EPS increased 4% to $5.37.

•Advanced our proven growth strategy, launching a range of high-impact, innovative new products during the quarter. This included a number of analytical instruments introduced at the American Society for Mass Spectrometry conference, including the Thermo Scientific Stellar mass spectrometer, which validates proteins of clinical interest discovered through our groundbreaking Thermo Scientific Orbitrap Astral mass spectrometer; and three new built-for-purpose editions of the Thermo Scientific Orbitrap Ascend Tribrid mass spectrometer tailored to MultiOmics, Structural Biology and BioPharma applications. To help our customers meet their sustainability goals, we also launched: a first-of-its-kind biobased film for our bioprocessing containers, which uses plant-based materials to deliver lower-carbon solutions in the manufacturing of therapies; and a new line of ENERGY STAR-certified Thermo Scientific TSX Universal Series ULT Freezers, which deliver industry-leading performance and energy efficiency.

•Continued to strengthen our industry-leading commercial engine and deepen our trusted partner status with customers to accelerate their innovation and enhance their productivity. In the quarter, we expanded our leading clinical trial supply services with a new ultra-cold facility in Bleiswijk, the Netherlands and a new state-of-the-art innovation lab at our site in Center Valley, Pennsylvania, to enable our pharmaceutical and biotech customers to accelerate the development of therapies and medicines. Also in the quarter, to support Indonesia’s growing investments in healthcare, scientific research, and renewable energy, we expanded our presence and capabilities in the country, further demonstrating our relevance to customers around the world.

•Shortly after the quarter ended, we completed our acquisition of Olink, a provider of differentiated next-generation proteomic solutions. The addition of Olink’s technology extends our capabilities and further advances our leadership position in protein research,enabling our customers to meaningfully accelerate discovery and scientific breakthroughs while delivering on the promise of precision medicine.

"Our excellent execution enabled us to deliver another quarter of strong financial performance and share gain," said Marc N. Casper, chairman, president, and chief executive officer of Thermo Fisher Scientific. "We continue to see the benefit of our proven growth strategy and the impact of our PPI Business System in our performance. Shortly after the quarter ended, we were also pleased to welcome our Olink colleagues to Thermo Fisher and are excited about the power of this new combination to better serve our customers and advance science."

Casper added, "We have made very good progress through the halfway point of the year and are in a great position to deliver differentiated performance in 2024. We’ve further extended our industry leadership and positioned our company for an even brighter future."

Second Quarter 2024

Revenue for the quarter declined 1% to $10.54 billion in 2024, versus $10.69 billion in 2023. Organic revenue was 1% lower and Core organic revenue growth was flat.

GAAP Earnings Results

GAAP diluted EPS in the second quarter of 2024 increased 15% to $4.04, versus $3.51 in the same quarter last year. GAAP operating income for the second quarter of 2024 grew to $1.82 billion, compared with $1.58 billion in the year-ago quarter. GAAP operating margin increased to 17.3%, compared with 14.8% in the second quarter of 2023.

Non-GAAP Earnings Results

Adjusted EPS in the second quarter of 2024 increased 4% to $5.37, versus $5.15 in the second quarter of 2023. Adjusted operating income for the second quarter of 2024 was $2.35 billion, compared with $2.37 billion in the year-ago quarter. Adjusted operating margin increased to 22.3%, compared with 22.2% in the second quarter of 2023.

Annual Guidance for 2024

Thermo Fisher is raising its full-year revenue and adjusted EPS guidance. The company is raising its revenue guidance to a new range of $42.4 to $43.3 billion versus its previous guidance of $42.3 to $43.3 billion. The company is raising its adjusted EPS guidance to a new range of $21.29 to $22.07 versus its previous guidance of $21.14 to $22.02.

Step Pharma announces publication in Haematologica of key data supporting CTPS1 inhibition as a therapeutic target in blood cancer

On July 24, 2024 Step Pharma, the world leader in CTPS1 inhibition for the targeted treatment of cancer, reported the publication in the August edition of Haematologica of preclinical data from the University of Nantes (CRCI2NA) further supporting the therapeutic activity of Step’s highly selective CTPS1 inhibitors in the treatment of blood cancers (Press release, Step Pharma, JUL 24, 2024, View Source [SID1234645044]).

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The therapeutic activity was observed for mantle cell lymphoma (MCL), including difficult-to-treat in vitro and in vivo models. Furthermore, Step Pharma’s CTPS1 inhibitors show significant synergy when combined with venetoclax, a selective BCL2 inhibitor that is commonly used to treat certain types of lymphoma and leukaemia.

CTPS1, an enzyme crucial in pyrimidine synthesis, plays a significant role in cancer cell proliferation. Step Pharma’s compounds selectively inhibit the de novo pyrimidine synthesis pathway by targeting CTPS1, providing a novel approach to cancer treatment. The Company’s lead asset, dencatistat (STP938), a first-in-class, highly selective, orally bioavailable CTPS1 inhibitor, is currently in phase 1 clinical development for T cell and B cell lymphoma (NCT05463263) with study sites open in France, the UK, and the USA.

MCL accounts for approximately 5% of B cell lymphoma. Despite recent advancements in the treatment of MCL, there is still an unmet clinical need for those who have not responded to Bruton’s Tyrosine Kinase (BTK) inhibitor therapy.

Andrew Parker, Chief Executive Officer of Step Pharma, commented

"The publication in Haematologica of these preclinical data provides additional evidence of the importance of inhibiting CTPS1 for the treatment of blood malignancies, including T and B cell lymphoma. The findings further support our approach as we continue to progress our phase 1 trial to develop targeted and efficient treatment options for individuals with blood cancer."

David Chiron, CNRS researcher at CRCI2NA, Nantes University, added

"These data represent a significant advancement in our understanding of blood cancer biology, particularly regarding the role of CTPS1. Our research on inhibiting CTPS1 emphasises the potential of this approach to fill an important gap in current treatment methods. These findings support the targeted inhibition of CTPS1 as a promising therapeutic strategy and pave the way for further research to gain a deeper understanding of its role and broader applications in different types of blood cancers."

Sonnet BioTherapeutics Reports Encouraging Data from Phase 1b/2a Clinical Trial of SON-080 in Chemotherapy-Induced Peripheral Neuropathy (CIPN) That Support Advancement into Phase 2 Study

On July 24, 2024 Sonnet BioTherapeutics Holdings, Inc. (the "Company" or "Sonnet") (NASDAQ:SONN), a clinical-stage company developing targeted immunotherapeutic drugs, reported encouraging data from the Phase 1b portion of its Phase 1b/2a clinical trial evaluating SON-080 for the treatment of CIPN (the "SB211 study") (Press release, Sonnet BioTherapeutics, JUL 24, 2024, View Source [SID1234645043]). The SB211 study is a double-blind, randomized, controlled trial of SON-080 conducted at two sites in Australia in patients with persistent CIPN using a new proprietary version of recombinant human Interleukin-6 (rhIL-6) that builds upon previous work with atexakin alfa. The goal of the Phase 1b portion of the SB211 study was to confirm safety and tolerability before continued development in Phase 2. As previously announced in March 2024, a data and safety monitoring board reviewed the unblinded safety and tolerability of SON-080 in the first nine patients and concluded that the symptoms were tolerable in the initial patients and the study could proceed to Phase 2. Additionally, the Company participated in a Virtual Investor "What This Means" segment to further discuss the Phase 1b data and highlight what this means for its development program moving forward. Click here to access the segment.

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CIPN is a common side effect of many chemotherapeutic drugs that induce peripheral nerve damage. CIPN can last for weeks to years after treatment has ended and patients with CIPN often experience discomfort that can result in persistent, unbearable pain, as well as motor and autonomic dysfunction that may limit the duration of their cancer treatment. Conventional pain medications and opioids are often ineffective against peripheral neuropathy, creating a significant unmet need for new treatment options. Low dose IL-6 has been shown to stimulate peripheral nerve growth in preclinical models, thereby ameliorating motor and sensory functions and normalizing the associated pain or sensation disturbance of neuropathy.

"We believe this highly encouraging data bridges the large atexakin alfa historical safety database in cancer patients and is foundational in advancing the development of SON-080 to a Phase 2 study evaluating the neuroprotective and neuro-regenerative effects in DPN," said Pankaj Mohan, Ph.D., Sonnet Founder and Chief Executive Officer. "IL-6 is often dysregulated in diabetic patients, suggesting there is disease modifying potential for the application of rhIL-6 in DPN. Given the high prevalence of neuropathy in diabetes and the commensurate industry interest in this market, we have prioritized DPN as the best potential indication for Phase 2 development. We intend to seek a partnership to move the asset forward towards commercialization."

A total of 9 patients were randomized between two different SON-080 dose groups and placebo in this portion of the study. The treatment period was 12 weeks long and patients were followed-up for an additional 12 weeks.

The Phase 1b data demonstrated SON-080 was well-tolerated at both 20 µg and 60 µg/dose, which was about 10-fold lower than the maximum tolerated dose (MTD) for IL-6 that was established in previous clinical evaluations. Injection site erythema was the most prominent treatment-related adverse event irrespective of the dose of SON-080, and was transient and mild in all but one case at each dose, where it was moderate. Fatigue was reported occasionally and was more prominent at the higher dose. One patient who developed severe fatigue and stopped dosing after one month was in the low-dose group. Headache, dizziness, and chills were reported infrequently in the high-dose group; all were mild apart from a single moderate event with each symptom. All other adverse events were infrequent and mild.

"These data suggest possible benefits in humans with various types of peripheral neuropathy due to cancer and diabetes. Interleukin-6 has been extensively studied in cancer patients in the past, so the use of SON-080 in CIPN was expected to provide a similar adverse event profile at low doses," commented Richard Kenney, M.D., Sonnet’s Chief Medical Officer. "We now have a further understanding of the adverse event profile and the opportunity to look at preliminary efficacy trends. We look forward to initiating a Phase 2 study with a partner in the much larger DPN indication."

The Quality-of-Life Questionnaire-CIPN twenty-item scale (QLQ-CIPN20), a validated survey designed to assess cancer patients’ experience of symptoms and functional limitations related to CIPN, was used as the primary indicator of response. While the number of patients in each group was small, a trend toward improved scores within a month of starting therapy was seen for both dose groups as compared to placebo in the overall scores. This greater improvement with SON-080 persisted after the 12 weeks of therapy had stopped, while the placebo group scores returned to baseline. These results are in line with the preclinical model insights with low dose IL-6, although further work with larger clinical groups is needed to substantiate this trend.

Multiple cytokines were studied as part of the safety evaluation. There was no demonstrable drug effect on any of these inflammatory cytokine serum levels during or after therapy with SON-080. However, there was a dose-related increase in serum amyloid alpha that persisted during therapy, which returned to baseline once treatment was stopped. An expert consultant concluded that the degree of amyloid elevation seen in this study for 12 weeks should be benign.

For more information about the SB211 study, visit clinicaltrials.gov and reference identifier NCT05435742.

About SON-080 as a Therapeutic Drug Candidate

SB211 studied a low dose of rhIL-6 called SON-080 that has an amino acid sequence identical to the native molecule. The trial targets serum levels similar to those induced with moderate exercise, which triggers the natural healing of nerves, muscle, and bone. As a pleiotropic cytokine, native IL-6 participates in several physiological processes, including tissue repair, glucose homeostasis, and the innate immune response at lower levels, but it can result in acute pathological inflammation at higher serum levels. Preclinical models of CIPN and DPN show that low dose rhIL-6 has the potential to stimulate nerve regrowth to re-establish normal sensations, thereby reducing pain and normalizing some of the physiological conditions that had deteriorated due to nerve degeneration. Early versions of rhIL-6, including Serono’s atexakin alfa and others, have been tested in hundreds of patients with cancer, diabetes, idiopathic aplastic anemia, and in healthy controls, showing a maximum tolerated dose of 10 µg/kg three times a week (TIW). The IL-6-related fever, nausea, and vomiting that were prominent adverse events at doses over 2.5 µg/kg TIW were substantially reduced at lower doses.

About the SB211 Phase 1b/2a Trial

The SB211 study was primarily designed to evaluate the safety, PK, PD, and initial efficacy of two dose levels of SON-080 compared to placebo. The drug is self-administered subcutaneously three times a week in patients with CIPN lasting at least 3 months after chemotherapy. The study was conducted at multiple sites in Australia, in a blinded fashion, comparing SON-080 to placebo. The primary endpoint explores the safety and tolerability of SON-080, with key secondary endpoints intended to measure PK, PD, and immunogenicity. Preliminary efficacy is being explored using standardized quality of life and pain questionnaires over the course of the trial.

Palvella Therapeutics and Pieris Pharmaceuticals Announce Definitive Merger Agreement

On July 24, 2024 Palvella Therapeutics, Inc. (Palvella), a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapies to treat patients suffering from serious, rare genetic skin diseases for which there are no U.S. Food and Drug Administration (FDA)-approved therapies, and Pieris Pharmaceuticals, Inc. (Nasdaq: PIRS) (Pieris) reported they have entered into a definitive merger agreement to combine the companies in an all-stock transaction (Press release, Pieris Pharmaceuticals, JUL 24, 2024, View Source [SID1234645042]). The combined company will focus on developing and commercializing Palvella’s lead clinical product candidate, QTORIN 3.9% rapamycin anhydrous gel (QTORIN rapamycin), for the treatment of microcystic lymphatic malformations (microcystic LMs), cutaneous venous malformations, and other serious, functionally debilitating skin diseases driven by the overactivation of the mammalian target of rapamycin (mTOR) pathway. Upon completion of the proposed merger, the combined company will operate under the name Palvella Therapeutics, Inc., will be headquartered in Wayne, PA, and is expected to trade on The Nasdaq Capital Market (Nasdaq).

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In connection with the proposed merger, Palvella has secured commitments from a syndicate of leading healthcare-dedicated investors in an oversubscribed $78.9 million concurrent private financing co-led by BVF Partners, L.P., an existing investor, and Frazier Life Sciences, a new investor. Additional new investors include Blue Owl Healthcare Opportunities, Nantahala Capital, DAFNA Capital Management, ADAR1 Capital Management, and a healthcare dedicated fund. Existing investors Samsara BioCapital, Petrichor, CAM Capital, Ligand Pharmaceuticals (Nasdaq: LGND), Integrated Finance Group (an AscellaHealth partner company), BioAdvance, and Gore Range Capital also committed to participate in the financing. The concurrent private financing includes approximately $18.9 million in principal and interest from Palvella convertible notes that will be funded prior to the close and convert into shares of common stock of the combined company. The concurrent private financing is expected to close immediately following the completion of the proposed merger.

The combined company is expected to have approximately $80.5 million of cash and cash equivalents at closing of the proposed merger and concurrent private financing, inclusive of the net proceeds expected to be received in the concurrent private financing and after deducting operating expenses incurred prior to closing and estimated transaction expenses. These cash resources are expected to be used to advance Palvella’s product candidate QTORIN rapamycin through multiple clinical data milestones and are expected to fund the combined company’s operations into the second half of 2027. The proposed merger and concurrent private financing are expected to close in the fourth quarter of 2024, subject to stockholder approval of both companies, the effectiveness of a registration statement to be filed with the U.S. Securities and Exchange Commission (SEC) to register the shares of Pieris common stock to be issued in connection with the merger, and the satisfaction of customary closing conditions. Pieris pre-merger stockholders will also be issued a contingent value right (CVR) representing the right to receive payments from proceeds received by the combined company, if any, under Pieris’ existing partnership agreements with Pfizer and Boston Pharmaceuticals.

"We are pleased to announce our merger with Pieris, allowing Palvella to become a publicly traded company and pursue our vision of becoming the leading rare disease company focused on developing and commercializing novel therapies to treat patients suffering from serious, rare genetic skin diseases," said Wes Kaupinen, Founder and Chief Executive Officer (CEO) of Palvella. "The expected proceeds from the merger and concurrent private financing are expected to fund us through multiple clinical trial milestones, including generating results from the single-arm, baseline-controlled Phase 3 clinical trial of QTORIN rapamycin for the treatment of microcystic lymphatic malformations, a serious, rare and chronically debilitating genetic disease for which there are currently no FDA-approved therapies."

"This transaction represents Pieris’ deep commitment to delivering value to its stockholders by preserving the future potential milestone and royalty streams from our partnered immuno-oncology bispecifics franchise for Pieris legacy stockholders through the CVRs, while also providing the opportunity for upside in an attractive, late-stage, rare disease company," said Stephen S. Yoder, President and CEO of Pieris. "With the anticipated funding and an accomplished management team, we believe Palvella is well-positioned to advance a Phase 3 clinical program with the FDA’s Breakthrough, Fast Track, and Orphan Drug Therapy Designations. This transaction is the culmination of a comprehensive review of strategic alternatives, and our board of directors believes that the merger with Palvella is in the best interests of our stockholders."

Palvella’s QTORIN Platform and QTORIN rapamycin

Palvella’s research team developed QTORIN, a patented and versatile platform designed to generate novel topical therapies that penetrate the deep layers of the skin to locally treat a broad spectrum of serious, rare genetic skin diseases.

QTORIN rapamycin is the lead product candidate from Palvella’s QTORIN platform. QTORIN rapamycin is a novel, patented 3.9% rapamycin anhydrous gel, which aims to harness the potential therapeutic benefits of rapamycin, an mTOR inhibitor, while minimizing systemic exposure of rapamycin and potential adverse reactions associated with systemic therapy. QTORIN rapamycin is currently under development for the treatment of microcystic LMs, cutaneous venous malformations, and other serious, functionally debilitating skin diseases driven by the overactivation of the mammalian target of rapamycin (mTOR) pathway. QTORIN rapamycin is protected by multiple issued composition patents in the U.S. and Japan and pending patent applications broadly covering anhydrous gel formulations of rapamycin in the U.S., Europe, and Japan.

QTORIN Rapamycin for the Treatment of Microcystic LMs

Palvella initiated research on QTORIN rapamycin as a targeted therapy for microcystic LMs in 2017 based on scientific insights implicating abnormal activation of the mTOR pathway in this disease. Microcystic LMs is a rare, chronically debilitating genetic disease caused by dysregulation of the phosphatidylinositol 3-kinase (PI3K)/mTOR pathway. The disease is characterized by malformed lymphatic vessels that protrude through the skin and persistently leak lymph fluid (lymphorrhea) and bleed, often leading to recurrent serious infections and cellulitis. The natural history of microcystic LMs is progressive, with symptoms generally worsening during life, including increases in the number and size of malformed vessels that lead to complications and lifetime morbidity. There are currently no FDA-approved treatments for the estimated more than 30,000 diagnosed patients with microcystic LMs in the United States.

In November 2023, based on Phase 2 clinical trial results, Palvella received FDA Breakthrough Therapy Designation for QTORIN rapamycin for microcystic LMs. Palvella previously announced positive topline Phase 2 clinical trial results from the multi-center, open-label study of 12 subjects receiving QTORIN rapamycin once-daily for 12-weeks. The Phase 2 clinical trial featured multiple pre-specified efficacy assessments, including clinician and patient global impression assessments as well as assessments of individual clinical manifestations that are important disease burdens for individuals living with microcystic LMs. All participants in the Phase 2 clinical trial demonstrated improvements on the Clinician Global Impression of Change scale, with all participants in the study rated as either "Much Improved" (n=7, 58%) or "Very Much Improved" (n=5, 42%) after 12-weeks of treatment compared to the pre-treatment baseline period. In addition to Breakthrough Therapy Designation, the FDA has granted both Fast Track Designation and Orphan Drug Designation to QTORIN rapamycin for the treatment of microcystic LMs.

In February 2023, Palvella had an End of Phase 2 meeting and, in April 2024, a Type B Breakthrough Therapy Designation meeting with FDA regarding the clinical trial program. Palvella considered FDA feedback on study ethics and other considerations related to selection of key study design features, site feedback on study ethics and feasibility, and input from expert regulatory advisors, and Palvella initiated SELVA, a 24-week, pivotal Phase 3, single-arm, baseline-controlled clinical trial of QTORIN rapamycin for the treatment of microcystic LMs, in the third quarter of 2024. The study’s primary and key secondary endpoints are clinician-reported outcomes and will enroll 40 subjects at leading vascular anomaly centers across the U.S.

QTORIN Rapamycin for the Treatment of Cutaneous Venous Malformations

Palvella is also developing QTORIN rapamycin for the treatment of cutaneous venous malformations. Cutaneous venous malformations are a rare genetic disease that results from overactivation of the PI3K/mTOR signaling pathway in the development of the venous network, leading to dilated and dysfunctional veins within the skin. Cutaneous venous malformations cause functional impairment, significantly impact quality of life, and are associated with severe long-term complications. In April 2024, the FDA granted Fast Track Designation to QTORIN rapamycin for the treatment of venous malformations. Palvella plans to initiate a Phase 2 baseline-controlled clinical trial of QTORIN rapamycin for the treatment of cutaneous venous malformations in the second half of 2024.

About the Proposed Merger

Under the terms of the merger agreement, Pieris will issue shares of Pieris common stock to pre-merger Palvella stockholders as merger consideration in exchange for the cancellation of shares of capital stock of Palvella, and Palvella will become a wholly-owned subsidiary of Pieris.

Pre-merger Pieris stockholders are expected to own approximately 18% of the combined company and pre-merger Palvella stockholders are expected to own approximately 82% of the combined company, in each case, prior to the issuance of the shares under the concurrent private financing. The percentage of the combined company that pre-merger Palvella stockholders and pre-merger Pieris stockholders will own upon the closing of the merger is subject to further adjustment based on the amount of Pieris’ net cash at the time of closing. In connection with the closing of the proposed transactions under the merger agreement, Pieris pre-merger stockholders will also be issued a contingent value right (CVR) representing the right to receive payments from proceeds received by the combined company, if any, under Pieris’ existing partnership agreements with Pfizer and Boston Pharmaceuticals, in addition to other potential licensing agreements involving certain of Pieris’ legacy assets, as well as certain potential payments related to historical research and development tax credits, which may or may not be realized.

The transactions contemplated by the merger agreement have been unanimously approved by the boards of directors of both companies and are expected to close in the fourth quarter of 2024, subject to approvals by the stockholders of each company, the effectiveness of a registration statement to be filed with the SEC to register the shares of Pieris common stock to be issued in connection with the merger, and other customary closing conditions. Additional information about the transaction will be provided in a Current Report on Form 8-K that will be filed by Pieris with the SEC and will be available at www.sec.gov.

Management and Organization

Following the merger, the combined company will be led by Wes Kaupinen, Founder and CEO of Palvella, and other members of the Palvella management team. The combined company’s board of directors will be comprised of four of the current directors of Palvella’s board of directors, and one director designated from Pieris’ current board of directors, who is expected to be Christopher Kiritsy, the chair of Pieris’ audit committee. Pieris will be renamed "Palvella Therapeutics, Inc."

Conference Call Information

The companies will host a webcast call and presentation to discuss the proposed transactions, as well as Palvella’s pipeline assets on Wednesday, July 24 at 8:30 am ET. The live webcast can be accessed here and on the Pieris website at www.pieris.com/investors in the ‘Investors’ section or by calling 877-407-8920 or +1 412-902-1010. A replay of the webcast will be archived and available following the event.

Advisors

TD Cowen is serving as lead placement agent and Cantor is serving as a placement agent for Palvella’s planned concurrent financing. Troutman Pepper Hamilton Sanders LLP is serving as legal counsel to Palvella. Cooley LLP is serving as legal counsel to the placement agents. Stifel is serving as the exclusive financial advisor to Pieris and Mintz, Levin, Cohn, Ferris, Glovsky, and Popeo, P.C. is serving as legal counsel to Pieris.