On June 17, 2021 BioNTech SE (NASDAQ: BNTX, "BioNTech" or "the Company"), reported that the first patient has been treated in its BNT111 Phase 2 cancer vaccine trial (2020-002195-12; NCT04526899)(Press release, BioNTech, JUN 18, 2021, View Source [SID1234584122]). The study is evaluating the Company’s therapeutic cancer vaccine candidate BNT111 in combination with Libtayo (cemiplimab) in patients with anti-PD1-refractory/relapsed unresectable Stage III or IV melanoma. BNT111 is the lead product candidate from BioNTech’s FixVac platform that targets a fixed combination of mRNA-encoded, tumor-associated antigens with the objective of triggering a strong and precise immune response against cancer and is fully owned by BioNTech.

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The BNT111-01 trial which is being conducted in collaboration with Regeneron, was reviewed and approved by the regulatory authorities in Spain, Germany, Italy and Poland as well as in the United Kingdom, the United States and Australia. The open-label randomized trial evaluates the efficacy, tolerability, and safety of BNT111 in combination with Libtayo, an anti-PD-1 monoclonal antibody, being co-developed by Regeneron and Sanofi. The trial is enrolling a total of 120 patients and will evaluate the effects of the combination as well as single agents alone. The primary endpoint is the overall response rate of BNT111 in combination with Libtayo. Secondary endpoints include overall response rate in the single agent arms, duration of response, and safety. The first patient has been dosed in the EU. BioNTech retains global commercial rights to BNT111.

"Our vision is to harness the power of the immune system against cancer and infectious diseases. We were able to demonstrate the potential of mRNA vaccines in addressing COVID-19. We must not forget, that cancer is also a global health threat, even worse than the current pandemic," said Özlem Türeci, M.D., Co-founder and Chief Medical Officer of BioNTech. "BNT111 has already shown a favorable safety profile and encouraging preliminary results in early clinical evaluation. With the start of patient treatment in our Phase 2 trial, we are encouraged to continue on our initial path to realize the potential of mRNA vaccines for cancer patients."

BNT111 is an intravenous therapeutic cancer vaccine candidate encoding for a fixed set of four cancer-specific antigens optimized for immunogenicity and delivered as RNA-lipoplex formulation. More than 90% of melanomas in patients express at least one of the four tumor-associated antigens encoded in BNT111 (NY-ESO-1, MAGE-A3, tyrosinase, and TPTE). BNT111 is one of the most advanced of five clinical-stage FixVac product candidates within BioNTech’s development pipeline.

This Phase 2 clinical trial is based on previous results from the Phase 1 Lipo-MERIT dose escalation trial (NCT02410733) that demonstrated a favorable safety profile in 89 patients with advanced melanoma. In addition, efficacy analysis of the Lipo-MERIT study in a subset of 42 metastatic melanoma patients previously treated with a checkpoint-inhibitor (CPI) showed that BNT111 mediated durable responses both as a single agent and in combination with anti-PD-1 antibodies and that durable objective responses by BNT111 were associated with activation and strong expansion of tumor-antigen-specific CD4+ and CD8+ T cells. These results were published in Nature in July 2020.

The Company also plans to start randomized Phase 2 trials with mRNA vaccine product candidates in two additional programs in 2021 (FixVac: BNT113 and iNeST: BNT122). As part of its development strategy, BioNTech aims to rapidly advance its broad oncology pipeline and expects to bring additional candidates into late-stage clinical development and towards market entry within the next five years.

About FixVac
BioNTech’s FixVac platform candidates consist of a fixed combination of mRNA-encoded non-mutated antigens shared within specific cancer types. They feature the Company’s proprietary RNA-lipoplex delivery formulation which is designed to enhance stability and translation of the mRNA cargo as well as specifically target dendritic cells. Thus, the vaccine candidate aims to trigger a strong and precise innate and adaptive immune response against cancer cells overexpressing the respective antigen.

On June 18, 2021 Protagonist Therapeutics, Inc. (Nasdaq:PTGX), a clinical stage biopharmaceutical company, reported the closing of its previously announced underwritten public offering of 3,503,311 shares of its common stock, including 456,953 shares sold pursuant to the underwriters’ exercise in full of their "green shoe" option to purchase additional shares, at a price to the public of $37.75 per share (Press release, Protagonist, JUN 18, 2021, View Source [SID1234584140]). Aggregate gross proceeds to Protagonist from the offering were approximately $132.2 million, before deducting underwriting discounts and commissions and offering expenses.

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J.P. Morgan Securities LLC, Jefferies LLC and Piper Sandler acted as joint book-running managers for the offering. JMP Securities LLC and H.C. Wainwright & Co., LLC acted as co-lead managers for the offering.

A shelf registration statement relating to the offered shares of common stock was filed with the Securities and Exchange Commission (SEC) on December 10, 2020. A final prospectus supplement and accompanying prospectus relating to the offering have been filed with the SEC and is available on the SEC’s website, located at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus related to the offering may be obtained, when available, from J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, by telephone at 866-803-9204, or by email at [email protected]; Jefferies LLC (Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, New York 10022; telephone: 877-821-7388; email: [email protected]); or Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, by telephone at (800) 747-3924 or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of, these securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On June 17, 2021 Artios Pharma Limited (Artios), a leading DNA Damage Response (DDR) company exploiting a broad DDR-based platform and small molecule drug design capabilities to develop a diverse pipeline of product candidates for the treatment of cancer, reported the publication of a peer reviewed article titled, "Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance" in Nature Communications(Press release, Artios Pharma, JUN 17, 2021, View Source [SID1234584104]). Using novel small molecule tool compounds, the preclinical data generated in collaboration with researchers at the Institute for Cancer Research, London, and Cancer Research U.K., validates the Company’s approach to developing a potential first-in-class Polθ inhibitor, which demonstrated potent, selective Polθ inhibition, BRCA-gene synthetic lethality in a potentially PARP-resistant setting, and PARP inhibitor synergy.

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Professor Chris Lord, Professor of Cancer Genomics at The Institute of Cancer Research, London and study co-leader, said: "Polθ is an ideal DNA damage response drug target as it is tumor specific, overexpressed in many tumors and found at low levels in healthy tissues. These results show that Polθ inhibitors exhibited exquisite selectivity and on-target activity, affecting only Polθ-Mediated End Joining and not other forms of DNA repair. This specificity, combined with demonstrated synthetic lethality with BRCA mutations, as well as synergy with a PARP inhibitor, suggest small molecule Polθ inhibition has broad utility for targeted clinical development in genetic backgrounds that are reliant on Polθ activity. I look forward to seeing how Polθ inhibitors perform in clinical trials and hope they will be able to benefit patients by opening up a new way of overcoming drug resistance."

Dr. Graeme Smith, Chief Scientific Officer of Artios Pharma, said: "This preclinical dataset further strengthens the scientific foundation of our Polθ inhibitor program. This publication is a testament to the deep scientific heritage and expertise in DNA damage response that drives the Artios discovery platform and pipeline. The extensive efforts of our team have delivered insights into the genetics and mechanisms that underlie the activity of Polθ inhibitors, leaving us well positioned to pursue a strategic development plan in the clinic across a wide range of opportunities."

Dr. Niall Martin, Chief Executive Officer at Artios Pharma, said: "These published results provide a clear rationale for three high-value opportunities for Polθ inhibitors: in the monotherapy setting to treat Polθ dependent cancers; in combination with PARP inhibitors to expand the utility of this important drug class; and in combination with DNA damaging therapies such as ionizing radiation to provide effective and widespread use of these agents. We are on track to launch our Polθ clinical program before year end, building upon our strong execution which includes strategic partnerships with Merck KGaA and Novartis, and our ongoing Phase 1 study of ART0380, a potential best-in-class ATR inhibitor."

Publication highlights include:

• Artios’ small molecule Polθ inhibitors provided nanomolar potent, selective, allosteric inhibition of the polymerase function of DNA polymerase Polθ, selectively inhibiting Theta-Mediated End Joining DNA repair without targeting Non-Homologous End Joining or Homologous Recombination.
• Inhibiting Polθ elicited DNA damage and synthetic lethality in BRCA1- or BRCA2-mutant tumor cells and enhanced the effects of a PARP inhibitor.
• Genetic screening revealed defects in the Shieldin complex causing both PARP inhibitor resistance and synthetic lethality with Polθ inhibition, thus identifying a subset of PARP inhibitor resistant disease with the potential to be specifically targeted with Polθ inhibitors.
• Sensitivity of BRCA1, Shieldin-defective tumours to Polθ inhibition was confirmed in vivo laying the foundations for preclinical and clinical development.

On June 17, 2021 Amneal Pharmaceuticals, Inc. (NYSE: AMRX) ("Amneal" or the "Company") reported the U.S. Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) for Bevacizumab, pursuant to Section 351(k) pathway of the Public Health Service Act, and with a standard review goal date in the second quarter of 2022 according to the BsUFA (Biosimilar User Fee Act) (Press release, Amneal Pharmaceuticals, JUN 17, 2021, View Source [SID1234584162]).

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The biosimilar was developed in collaboration with mAbxience, a Spain-based biotechnology company. Bevacizumab is the biosimilar version of Avastin and when approved will be marketed under the proprietary name AlymsysTM. Alymsys was approved by the European Medicines Agency (EMA) in February 2021. Amneal and mAbxience believe that the data supports the biosimilarity of its AlymsysTM product to Avastin.

"The FDA’s acceptance of our BLA for Bevacizumab is a significant milestone in our journey to become an important player in biosimilars," stated Chirag and Chintu Patel, Co-Chief Executive Officers. As previously announced, the Company expects its initial biosimilar portfolio will include Filgrastim (biosimilar for Neupogen), Pegfilgrastim (biosimilar for Neulasta) and Bevacizumab (biosimilar for Avastin).

Bevacizumab is a vascular endothelial growth factor inhibitor. Amneal is seeking approval for Bevacizumab for the treatment of metastatic colorectal cancer, in combination with intravenous fluorouracil-based chemotherapy for first- or second-line treatment and metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first line Alymsys-containing regimen. Amneal also intends to seek approval for the remainder of the indications from the reference product label as soon as possible, subject to patent and regulatory exclusivities, by the biosimilarity pathway pursuant to Section 351(k).

According to IQVIA, a leading healthcare data and analytics provider, U.S. annual sales for Bevacizumab for the 12 months ended April 2021 were approximately $2.8 billion.

On June 17, 2021 CytoReason, an AI company developing a computational disease model of the human body for clinical drug development, reported the initiation of a project with French global biopharmaceutical company Sanofi, which will utilize its cell-centered models and deconvolution techniques to suggest mechanistic insights for each asthma endotype (Press release, CytoReason, JUN 17, 2021, View Source [SID1234597888]).

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The focus of this project is to gain clarity on the heterogeneity of asthma patients, with the goal of identifying stable and reproducible asthma endotypes, as well as associated diagnostic features, using minimal invasive procedures. For this project, CytoReason’s AI platform will use one of the most comprehensive datasets in moderate to severe asthma, covering samples from both adults and children.

Asthma is a complex disease with genetic and environmental factors that lead to airway inflammation, resulting in excess mucus in a patient’s airway, which causes coughing, wheezing and shortness of breath. It can appear in several degrees of severity, ranging from mild to severe, and can be classified as either Type 2 asthma, which includes allergic and eosinophilic asthma, or non-Type 2 asthma, which is associated with low eosinophil counts often presented with altered innate immune response and activation of Th17 cells. Though symptoms of the disease can often be controlled, asthma, which is a key area of research for Sanofi, cannot be completely cured. One of the main challenges in the disease is classification of patients to find the most suitable treatment.

"We are very excited to be launching our collaboration with Sanofi," said David Harel, CEO and Co-founder of CytoReason. "It represents a chance to make a real difference in driving better understanding of the heterogeneous and complex nature of asthma and its diversified manifestation in patients. Additionally, the work we do with Sanofi could enhance future research in this field and could inform precision medicine strategies for improved patient benefit."