On February 1, 2021 ENB Therapeutics, Inc., a biotechnology company pioneering a new and differentiated class of therapeutics targeting the ETB receptor (ETBR), reported the successful completion of the third dosing cohort in a Phase I dose escalation clinical trial of ENB-003 in combination with pembrolizumab (Press release, ENB Therapeutics, FEB 1, 2021, View Source [SID1234634064]). Doses of ENB-003 administered to date appear well-tolerated and as the trial progressed into the anticipated therapeutic range of ENB-003 has demonstrated its first efficacy signal as was reported at the SITC (Free SITC Whitepaper) 2020 annual meeting. ENB-003 is a selective and potent inhibitor of the ETBR receptor which is overexpressed in over 40% of all tumor types and blocks T-cell trafficking, thus creating "cold" tumors which have a high unmet need.

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"We are very excited to observe the continued safety of our combination regimen as well as early efficacy signals as we escalate the dose into the expected therapeutic window of ENB-003. Best overall responses of the 9 patients dosed to date include 4 SD (stable disease) and one PR (partial response) in a platinum refractory ovarian cancer subject who had a ~72% reduction in tumor burden with deepening of response and no disease progression at 6 months of therapy. Median PFS with pembrolizumab alone in recurrent ovarian cancer is 2.3 months," said Sumayah Jamal, MD-PhD, President, Co-Founder and CSO of ENB Therapeutics, Inc. "We are hoping for continued positive responses as we advance the trial and escalate the dose of ENB-003."

The Phase I/II multi-center, open-label trial of ENB-003 is currently enrolling patients with advanced solid tumors in indications associated with ETBR expression. The Phase I trial includes a monotherapy run-in followed by combination therapy. The Phase I dose escalation of ENB-003 in combination with pembrolizumab is primarily designed to assess safety and tolerability and to determine a recommended Phase II dose (RP2D). Following selection of an RP2D, we expect to initiate a Phase II dose expansion trial with the primary objective to evaluate ENB-003’s ability to enhance responsiveness to pembrolizumab in patients who have previously failed pembrolizumab therapy or have tumors associated with pembrolizumab resistance.

On February 1, 2021 The CiRA Foundation (CiRA_F) reported that it has signed the following two agreements with Thyas Co. Ltd. ("Thyas"; located in Sakyo-ku, Kyoto) (Press release, Thyas , FEB 1, 2021, View Source [SID1234629212]).

(1) Basic agreement on the manufacturing of autologous regenerated T cells by Thyas
(2) Joint research on the my iPS Project for the production of autologous regenerated T cells

(1) Basic agreement on the manufacturing of autologous regenerated T cells by Thyas
CiRA_F has conducted a basic agreement with Thyas to manufacture intravenous autologous iPS cellderived cytotoxic T cells (hereinafter referred to as "autologous regenerative T cells") for use in clinical trials. The term of the consignment is planned to be from March 2022 to February 2024, with aim for a clinical trial scheduled to start in the second half of 2022. Currently, Thyas and CiRA_F are negotiating the conclusion of a formal outsourcing contract.

It is said that thousands of cancer cells are generated every day in the body of a healthy person, but these cells are regularly eradicated by the immune system. If the immune function does not work properly, however, cancer cells persist and proliferate, eventually leading to cancer. In recent years, immunotherapies have been developed to treat cancer patients by strengthening their immune systems.

T cells are a type of white blood cell that attacks foreign substances in the body. However, T cells in cancer patients are chronically stimulated and exhausted by cancer cells. Professor Shin KANEKO and his colleagues at the Center for iPS Cell Research and Application (CiRA), Kyoto University, are using iPS cell technology to develop a new form of immunotherapy, in which T cells are reprogrammed into iPS cells, which are then expanded and differentiated into T cells that can effectively suppress cancer. As part of this research, they have developed a technology to manufacture such T cells in large quantities. Thyas is working with Professor Kaneko to put this technology into practical use by preparing autologous regenerated T cells.

(2) Joint research on the my iPS Project to produce autologous regenerated T cells
Currently, CiRA_F is working on the "my iPS Project", with the goal of delivering patient iPS cells and cells derived from them by 2025. Although it is possible to produce patient iPS cells, the current cost is about 40 million yen (about US$400,000) per production. In the my iPS Project, the CiRA_F aims to provide safe patient iPS cells at 1 million yen (around US$10,000) per case by automating the cell manufacturing and improving the efficiency of quality control.

In this joint research, Thyas and CiRA_F will study the manufacturing method so that patient iPS cells can be used as the raw material for autologous regenerated T cells. Specifically, biomarkers and other properties will be analyzed to evaluate the best iPS cell lines for T cell differentiation. Accordingly, the differentiation method of my iPS to T cells will also be intensively investigated.

The CiRA Foundation collaborates with academia and industry to provide iPS cell-derived regenerative medicines to clinical practice as soon as possible.

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On February 1, 2021 Zealand Pharma A/S ("Zealand") reported that it has today, as part of completion of a directed issue and private placement (the "Offering"), registered with the Danish Business Authority, the capital increase of DKK 3,600,841, divided into 3,600,841 ordinary shares (the "New Shares") (Press release, Zealand Pharmaceuticals, FEB 1, 2021, View Source [SID1234576927]).

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Following the registration of the New Shares with the Danish Business Authority, Zealand’s share capital amounts to DKK 43,400,547 divided into 43,400,547 shares with a nominal value of DKK 1 each.

The New Shares rank pari passu with Zealand’s existing shares and carry the same dividend and other rights. Each New Share carries one vote at Zealand’s general meetings. Zealand only has one class of shares.

The New Shares have been issued under a temporary ISIN code and are expected to be admitted to trading on Nasdaq Copenhagen on 2 February 2021 in Zealand’s permanent ISIN code DK0060257814. The temporary ISIN code is expected to be merged with the permanent ISIN code on 3 February 2021.

The amendments to Zealand’s articles of association required by the capital increase have been registered today with the Danish Business Authority.

Managers and legal counsels:

Goldman Sachs International, Jefferies GmbH and Danske Bank A/S (the "Joint Global Coordinators") are acting as joint global coordinators and joint bookrunners in the Offering, and Bryan, Garnier & Co. and Nordea Danmark, Filial af Nordea Bank Abp, Finland are acting as co-managers in the Offering (the Joint Global Coordinators and the co-managers are jointly referred to as the "Managers"). Danske Bank A/S is acting as settlement agent for the Offering.

On February 1, 2021 Sonnet BioTherapeutics Holdings, Inc., (NASDAQ:SONN) a clinical-stage company developing targeted immunotherapeutic drugs, reported that it has successfully completed a non-human primate (NHP) repeat-dose study of SON-1010, a proprietary fully human Interleukin 12 (IL-12) therapeutic candidate configured using Sonnet’s Fully Human Albumin Binding (FHAB) platform (Press release, Sonnet BioTherapeutics, FEB 1, 2021, View Source [SID1234576687]). The FHAB technology targets tumor tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of immunomodulatory cytokines.

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The objectives of the study were to evaluate the toxicity of SON-1010 in a repeat dose regimen at two different doses and to gather critical data for the design of further IND-enabling safety and toxicity studies. The study included both intravenous and subcutaneous routes of administration with a total of two doses given 14 days apart. The high dosage rate utilized in this study was greater than 50 times the anticipated clinical level of exposure to patients.

Study results included:

Repeat dosing by intravenous and subcutaneous routes of administration were tolerated at both dose levels examined. As is typically observed with IL-12 administration, the white blood cell count dropped, and liver enzymes (ALT and AST) were elevated. These were transient effects that returned to baseline within 7 days following the second dose.
SON-1010-related changes in the physiological observations, body weight, pathology, cytokines and immunophenotyping were seen, all of which were consistent with those on-target effects previously observed in single dose studies.
A significant increase in Interferon-γ levels, a key pleiotropic cytokine associated with anti-tumor activity, was observed following the initial dose of SON-1010 with lower Interferon-γ levels observed following the second dose. This trend follows the published data from other studies of IL-12 in both humans and NHPs.
Pharmacokinetic analysis indicated a mean serum half-life of approximately 40 hours for animals administered SON-1010 via subcutaneous injection. This is consistent with data from the previously conducted dose escalation phase of the study, which demonstrates a substantial improvement in half-life compared to the 13-19-hour half-life of naked, recombinant human IL-12.
Pankaj Mohan, Ph.D., Sonnet founder and CEO, commented, "Taken in combination with our recent single dose toxicology results, these repeat dose data further reinforce our confidence in the SON-1010 safety and efficacy profile as we look forward to initiating the Phase 1 clinical development program later this year."

Sonnet used these data to inform the design of the ongoing GLP toxicity studies in preparation for IND submission. Additionally, the Company has developed a, continuous manufacturing platform consisting of an industry standard mammalian cell (Chinese Hamster Ovary or CHO) host cell line coupled with an intensified perfusion process that allows for rapid scale-up and commercial manufacturing, using state-of-the-art processes and technologies. The mammalian cell culture system enables glycosylation, thereby reducing the risk of immunogenicity.

Susan Dexter, Sonnet’s Chief Technology Officer added, "We have established an intensified, continuous manufacturing process, as compared with an industry standard fed batch process, to enhance productivity and improve the yield of difficult-to-express cytokines. We believe that the ability to manufacture SON-1010 as a single genetic sequence will enable scale up and optimize product quality. A lyophilization formulation provides stability and refrigerated cold chain simplicity."

On February 1, 2021 Revolution Medicines, Inc. (Nasdaq: RVMD) reported that it has commenced an underwritten public offering of 4,000,000 shares of common stock (Press release, Revolution Medicines, FEB 1, 2021, View Source [SID1234575012]). All of the shares of common stock are being offered by Revolution Medicines. In addition, Revolution Medicines intends to grant the underwriters a 30-day option to purchase up to an additional 600,000 shares of common stock.

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J.P. Morgan, Cowen, SVB Leerink and Guggenheim Securities are acting as the joint book-running managers for the proposed offering.

A registration statement relating to these securities has been filed with the Securities and Exchange Commission (SEC) but has not yet become effective. The offering is being made only by means of a prospectus, copies of which may be obtained, when available, from: J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (866) 803-9204, or by email at [email protected]; Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY, 11717, Attn: Prospectus Department, by email at [email protected] or by telephone at (833) 297-2926; SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA, 02110, by telephone at 1-800-808-7525, ext. 6105, or by email at [email protected]; or Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, NY 10017, by telephone at (212) 518-9544, or by email at [email protected].

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