On May 20, 2021, Pieris Pharmaceuticals, Inc. (the "Company") and Biotechnology Value Fund, L.P., Biotechnology Value Fund II, L.P., and Biotechnology Value Trading Fund OS, L.P. (collectively, "BVF") reported that entered into an Exchange Agreement (the "Exchange Agreement") pursuant to which BVF agreed to exchange (the "Exchange") an aggregate of 5,000,000 shares of the Company’s common stock, par value $0.001 ("Common Stock"), owned by BVF for an aggregate of 5,000 shares of the Company’s newly-designated Series E Convertible Preferred Stock, a "toothless" preferred stock, par value $0.001 per share ("Series E Preferred Stock") (Filing, 8-K, Pieris Pharmaceuticals, MAY 20, 2021, View Source [SID1234580441]). The Exchange closed on May 21, 2021.

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As described below, the Series E Preferred Stock has substantially the same terms as the Company’s Series D Convertible Preferred Stock, par value $0.001 per share ("Series D Preferred Stock"), issued in March 2020; Series C Convertible Preferred Stock, par value $0.001 per share ("Series C Preferred Stock"), issued in November 2019; Series B Convertible Preferred Stock, par value $0.001 per share ("Series B Preferred Stock"), issued in January 2019; and Series A Convertible Preferred Stock, par value $0.001 per share ("Series A Preferred Stock"), issued in June 2016, all currently held by entities affiliated with BVF. The shares of Series E Preferred Stock issued in the Exchange are convertible into an aggregate of 5,000,000 shares of Common Stock (subject to adjustment as provided in the Series E Certificate of Designation, as defined below), subject to a 9.99% beneficial ownership blocker provision described below.

As of the date of the Exchange Agreement, BVF represented to the Company that it beneficially owned 5,872,762 shares of Common Stock, representing approximately 9.28% of the shares of Common Stock outstanding as of such date. In addition, BVF holds (i) 2,907 shares of Series A Preferred Stock, which are convertible into 2,907,000 shares of Common Stock (subject to adjustment as provided in the Certificate of Designation of Series A Convertible Preferred Stock of Pieris Pharmaceuticals, Inc. (the "Series A Certificate of Designation")), subject to a 9.99% beneficial ownership blocker provision set forth in the Series A Certificate of Designation; (ii) 5,000 shares of Series B Preferred Stock, which are convertible into 5,000,000 shares of Common Stock (subject to adjustment as provided in the Certificate of Designation of Series B Convertible Preferred Stock of Pieris Pharmaceuticals, Inc. (the "Series B Certificate of Designation")), subject to a 9.99% beneficial ownership blocker provision set forth in the Series B Certificate of Designation; (iii) 3,522 shares of Series C Preferred Stock, which are convertible into 3,522,000 shares of Common Stock (subject to adjustment as provided in the Certificate of Designation of Series C Convertible Preferred Stock of Pieris Pharmaceuticals, Inc. (the "Series C Certificate of Designation")), subject to a 9.99% beneficial ownership blocker provision set forth in the Series C Certificate of Designation; and (iv) 3,000 shares of Series D Preferred Stock, which are convertible into 3,000,000 shares of Common Stock (subject to adjustment as provided in the Certificate of Designation of Series D Convertible Preferred Stock of Pieris Pharmaceuticals, Inc. (the "Series D Certificate of Designation")), subject to a 9.99% beneficial ownership blocker provision set forth in the Series D Certificate of Designation.

A copy of the Exchange Agreement is attached hereto as Exhibit 10.1 and is incorporated herein by reference. The foregoing is only a brief description of the material terms of the Exchange Agreement, does not purport to be complete and is qualified in its entirety by reference to the full text of the Exchange Agreement. The representations, warranties and covenants made by the Company in the Exchange Agreement were made solely for the benefit of the parties to the Exchange Agreement, including, in some cases, for the purpose of allocating risk among the parties thereto, and should not be deemed to be a representation, warranty or covenant to investors. Moreover, such representations, warranties or covenants were made as of May 20, 2021. Accordingly, such representations, warranties and covenants should not be relied on as accurately representing the current state of the Company’s affairs

On May 20, 2021 Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company focused on discovering and developing small molecule therapeutics targeting fundamental biological pathways of cancers, reported the closing of a $20 million Series A financing of Zentera Therapeutics, a biopharmaceutical company with headquarters in Shanghai, China (Press release, Zentera Therapeutics, MAY 20, 2021, View Source [SID1234585516]). Leading the financing is Tybourne Capital Management, a global investment manager headquartered in Asia, and joining the syndicate is OrbiMed Asia, a leading healthcare fund in Asia. Zentalis, through its wholly owned subsidiaries, remains the majority shareholder of Zentera.

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The proceeds from the Series A financing will be used to develop and commercialize three cancer therapies discovered by Zentalis, in addition to potential future candidates, in China. Anthony Sun, MD, CEO of Zentalis, will serve as CEO of Zentera.

"The launch of Zentera is a key milestone in our global clinical development strategy," commented Dr. Anthony Sun, Chairman and Chief Executive Officer at Zentalis Pharmaceuticals and Chief Executive Officer at Zentera Therapeutics. "As the second-largest pharmaceutical market in the world, establishing a joint venture in China is the first step toward advancing our product candidates on a global scale. Furthermore, we are building a management team in China of seasoned professionals who are passionate about improving cancer treatment. We would like to thank our partners, Tybourne Capital Management and OrbiMed Asia, for supporting our vision to efficiently advance our best-in-class therapies to markets worldwide."

Bosun Hau, Managing Director and Co-Head of Private Equity at Tybourne Capital Management, commented, "Over the past few years, we have watched Zentalis’ remarkable clinical progress in developing potentially best-in-class candidates for patients with cancer. We are pleased to work with Zentera, as we believe these therapies will greatly benefit patients internationally."

Dr. David Wang, Partner and Senior Managing Director at OrbiMed Asia, added, "At OrbiMed, we are passionate about investing in innovative solutions that improve the lives of patients. The establishment of this joint venture, which helps to bring potentially life-changing treatments to China, aligns with our values and we are delighted to add Zentera to the OrbiMed family."

Zentalis’ pipeline candidates that will be developed in China by Zentera include its oral SERD (ZN-c5), WEE1 inhibitor (ZN-c3), and BCL-2 inhibitor (ZN-d5), which address unmet medical needs in large patient populations in both solid and liquid tumors. Additional Zentalis candidates may also be developed in China by Zentera.

On May 20, 2021 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported interim results from the Phase III IMpower010 study, showing for the first time that treatment with Tecentriq (atezolizumab) following surgery and chemotherapy reduced the risk of disease recurrence or death (disease-free survival; DFS) by 34% (hazard ratio [HR]=0.66, 95% CI: 0.50–0.88) in people with Stage II-IIIA non-small cell lung cancer (NSCLC), whose tumours express PD-L1≥1%, compared with best supportive care (BSC) (Press release, Hoffmann-La Roche, MAY 20, 2021, View Source [SID1234580341]). In this population, median DFS was not yet reached for Tecentriq compared with 35.3 months for BSC.

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In the larger population of all randomised Stage II-IIIA study participants, Tecentriq reduced the risk of disease recurrence or death by 21% (HR=0.79, 95% CI: 0.64–0.96) after a median follow-up of 32.2 months.1 In this population, Tecentriq increased DFS by a median of seven months (42.3 months versus 35.3 months with BSC).1 Safety data for Tecentriq were consistent with its known safety profile and no new safety signals were identified. The full results of IMpower010 will be presented in the lung cancer oral abstract session (Abstract #8500) on Sunday 6 June (08:00–11:00 EDT) at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting.

"These landmark Phase III data demonstrate for the first time that cancer immunotherapy can bring a clinically meaningful improvement to certain people with early lung cancer in the adjuvant setting," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "These results lay the groundwork for a new approach to the treatment of early-stage lung cancer and bring us closer to our goal of providing an effective and tailored treatment option for every person diagnosed with this disease."

The goal of adjuvant therapy is to lower the risk of recurrence and provide the best opportunity for a cure. Still, about half of all patients with Stage I-III NSCLC eventually develop disease recurrence following curative-intent treatment.2 Adjuvant platinum-based chemotherapy is the current standard of care for patients with completely resected early-stage NSCLC (Stage IB-IIIA) who are at a high-risk of disease recurrence or relapse. This treatment provides a modest 4–5% improvement in five-year survival compared with observation.3

Follow-up will continue with planned analyses of DFS in the overall intent-to-treat (ITT) population, including Stage IB patients, which at the time of analysis did not cross the threshold, and overall survival (OS) data, which were immature at the time of interim analysis. In the overall randomised population of study participants, adverse events (AEs) occurred in 92.7% of people receiving Tecentriq, compared with 70.7% of those receiving BSC. Grade 3 or 4 events occurred in 21.8% of people treated with Tecentriq compared with 11.5% in the BSC group; 0.8% of people in the Tecentriq group experienced a Grade 5 AE. As anticipated, the addition of up to one year of Tecentriq following chemotherapy led to a higher number of AEs compared with BSC.

Tecentriq has previously shown clinically meaningful benefit in various types of lung cancer, with five currently approved indications in markets around the world. It was the first approved cancer immunotherapy for front-line treatment of adults with extensive-stage small cell lung cancer (SCLC) in combination with carboplatin and etoposide (chemotherapy). Tecentriq also has four approved indications in NSCLC as either a single agent or in combination with targeted therapies and/or chemotherapies. Tecentriq is available in three dosing options, providing the flexibility to choose administration every two, three or four weeks.

Roche has an extensive development programme for Tecentriq, including multiple ongoing and planned Phase III studies across different settings in lung, genitourinary, skin, breast, gastrointestinal, gynaecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines, as well as studies in metastatic, adjuvant and neoadjuvant settings across various tumour types.

About the IMpower010 study
IMpower010 is a Phase III, global, multicentre, open-label, randomised study evaluating the efficacy and safety of Tecentriq compared with BSC, in participants with Stage IB-IIIA NSCLC (UICC 7th edition), following surgical resection and up to 4 cycles of adjuvant cisplatin-based chemotherapy. The study randomised 1,005 people with a ratio of 1:1 to receive either at most 16 cycles of Tecentriq or BSC. The primary endpoint is investigator-determined DFS in the PD-L1-positive Stage II-IIIA, all randomised Stage II-IIIA and ITT Stage IB-IIIA populations. Key secondary endpoints include OS in the overall study population, ITT Stage IB-IIIA NSCLC.

Efficacy results

PD-L1 ≥1% Stage II-IIIA Randomised Stage II-IIIA ITT
Tecentriq (n=248) BSC (n=228) Tecentriq (n=442) BSC (n=440) Tecentriq (n=507) BSC (n=498)
Median DFS (months) NR 35.3 42.3 35.3 NR 37.2
Stratified HR (95% CI) 0.66 (0.50, 0.88) 0.79 (0.64, 0.96) 0.81 (0.67, 0.99)*
Stratified log-rank p-value (2-sided) 0.004 0.02 0.04
NR, not reached.
* Did not cross significance boundary.

Safety results

Tecentriq BSC
All Grade AEs 92.7% 70.7%
Grade 3-4 AEs 21.8% 11.5%
Grade 5 treatment-related AEs 0.8% n/a
AEs leading to treatment withdrawal 18.2% n/a
n/a, not applicable.

About NSCLC
Lung cancer is one of the leading causes of cancer death globally.4 Each year 1.8 million people die as a result of the disease; this translates into more than 4,900 deaths worldwide every day.4 Lung cancer can be broadly divided into two major types: NSCLC and SCLC. NSCLC is the most prevalent type, accounting for around 85% of all cases.5 NSCLC comprises non-squamous and squamous-cell lung cancer, the squamous form of which is characterised by flat cells covering the airway surface when viewed under a microscope.5

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called Programmed Death Ligand-1 (PD-L1), which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of NSCLC, SCLC, certain types of metastatic urothelial cancer, in PD-L1-positive metastatic triple-negative breast cancer and for hepatocellular carcinoma. In the US, Tecentriq is also approved in combination with Cotellic (cobimetinib) and Zelboraf (vemurafenib) for the treatment of people with BRAF V600 mutation-positive advanced melanoma.

About Roche in cancer immunotherapy
Roche’s rigorous pursuit of groundbreaking science has contributed to major therapeutic and diagnostic advances in oncology over the last 50 years, and today, realising the full potential of cancer immunotherapy is a major area of focus. With over 20 molecules in development, Roche is investigating the potential benefits of immunotherapy alone, and in combination with chemotherapy, targeted therapies or other immunotherapies with the goal of providing each person with a treatment tailored to harness their own unique immune system to attack their cancer. Our scientific expertise, coupled with innovative pipeline and extensive partnerships, gives us the confidence to continue pursuing the vision of finding a cure for cancer by ensuring the right treatment for the right patient at the right time.

In addition to Roche’s approved PD-L1 checkpoint inhibitor, Tecentriq (atezolizumab), Roche’s broad cancer immunotherapy pipeline includes other checkpoint inhibitors, such as tiragolumab, a novel cancer immunotherapy designed to bind to TIGIT, individualised neoantigen therapies and T-cell bispecific antibodies.

On May 20, 2021 Exact Therapeutics AS (Euronext Growth: EXTX), a clinical stage precision medicine company utilizing Acoustic Cluster Therapy (ACT) to harness the power of ultrasound in therapeutic amplification across multiple therapeutic areas and product classes, reported that an abstract describing the background and methodology of its Phase I study, ACTIVATE, has been released for publication at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, Exact Therapeutics, MAY 20, 2021, View Source [SID1234580358]).

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The ACTIVATE Study (NCT04021277) is the first in a series of clinical investigations planned of the Company’s Acoustic Cluster Therapy (ACT) platform technology for targeted therapeutic enhancement.

Abstract Title: Phase I trial of acoustic cluster therapy (ACT) with chemotherapy in patients with liver metastases of gastrointestinal origin (ACTIVATE study)

Oral Abstract Session: Trials in Progress, Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Abstract: TPS3145

Lead Author: Professor Udai Banerji, NIHR Professor of Molecular Cancer Pharmacology at The Institute of Cancer Research and Honorary Consultant in Medical Oncology, The Royal Marsden NHS Foundation Trust.

On May 20, 2021 Agenus (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of checkpoint antibodies, cell therapies, adjuvants, and vaccines designed to activate immune response to cancers and infections, reported data on the differentiated activity profile of balstilimab, an anti-PD-1 antibody, and new Phase 1 clinical data for AGEN2373, a CD137 agonist antibody, as published in abstracts for two posters to be presented at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2021 from June 4 – 8, 2021 (Press release, Agenus, MAY 20, 2021, View Source [SID1234580374]).

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Balstilimab has shown expanded clinical activity in a Phase 2 clinical trial for patients with recurrent or metastatic cervical cancer. Responses have been observed in both PD-L1 positive and PD-L1 negative tumors in contrast to approved anti-PD-1 antibodies which have shown almost no responses in the PD-L1 negative population. Preclinical observations using the company’s proprietary platform corroborate these results, showing differentiated activity and superior tumor killing potential for balstilimab as compared to commercially available anti-PD-1 antibodies.

Agenus submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) on April 19 for the use of balstilimab in patients with recurrent or metastatic cervical cancer. This submission was based on data from the Phase 2 trial showing a response rate of 20% in PD-L1 positive tumors and an overall response rate of 15% with a median duration of response of 15.4 months.

AGEN2373 is a conditionally active CD137 agonist antibody designed to overcome limitations seen with first-generation CD137 agonist antibodies, including the development of liver toxicity. In this first-in-human study of AGEN2373 in patients with advanced solid tumors, no dose limiting toxicities were seen at doses up to 3 mg/kg; notably, no liver toxicity has been observed. Five patients demonstrated stable disease out of 19 patients treated with AGEN2373 monotherapy, including one heavily pretreated patient with metastatic leiomyosarcoma who had progressed on prior combination checkpoint immunotherapy.

"We are encouraged by the differentiated qualities of our anti-PD-1 balstilimab both in the clinic and in preclinical models," said Steven O’Day, MD, Chief Medical Officer at Agenus. "Our novel CD137, AGEN2373, has been well tolerated in this dose escalation trial and we look forward to advancing it into combinations for potential benefit to patients."

Presentation Details:

Abstract title: Differentiated activity profile for the PD-1 inhibitor balstilimab
Abstract number: 5529
Poster Session: Gynecologic Cancer
Presenting author: Cailin Joyce, PhD

Abstract title: Initial findings of the first-in-human Phase I study of AGEN2373, a conditionally active CD137 agonist antibody, in patients (pts) with advanced solid tumors
Abstract number: 2634
Poster Session: Developmental Therapeutics—Immunotherapy
Presenting author: Anthony Tolcher, MD

The 2021 ASCO (Free ASCO Whitepaper) Annual Meeting will take place on June 4 – 8, 2021.

About balstilimab
Balstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4) designed to block PD-1 (programmed cell death protein 1) from interacting with its ligands PD-L1 and PD-L2. PD-1 is a negative regulator of immune activation that is considered a foundational target within the immuno-oncology market. Balstilimab is currently in clinical trials as monotherapy and in combination with Agenus’ anti-CTLA-4, zalifrelimab, in an ongoing Phase 2 study for recurrent/metastatic cervical cancer.

A Biologics License Application has been submitted to the U.S. Food and Drug Administration for the use of balstilimab to treat recurrent/metastatic cervical cancer.

About AGEN2373
AGEN2373 is a novel, fully human monoclonal conditionally active CD137 agonist antibody designed to selectively enhance CD137 co-stimulatory signaling in activated immune cells while mitigating side effects associated with systemic activation of CD137. CD137 (4-1BB) is a positive regulator of the immune system that is highly upregulated on activated T cells (adaptive immune cells) and NK cells (innate immune cells).

AGEN2373 is advancing in a Phase 1 clinical trial against solid tumors.