On October 21, 2021 Akeso, one of leading Chinese pharmaceutical innovation company reported that the first patient was dosed in a phase I clinical trial of the Company’s independently developed TIGIT monoclonal antibody (AK127) in combination with the Company’s global first-in-class Cadonilimab (PD-1/CTLA-4 bi-specific antibody,AK104) for the treatment of advanced or metastatic solid tumors in Australia (Press release, Akeso Biopharma, OCT 21, 2021, View Source [SID1234591731]).

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This is an open-label, multicenter phase I clinical trial designed to evaluate the safety, tolerability, pharmacokinetic, immunogenicity, pharmacodynamics and anti-tumor activity of AK127 in combination with Cadonilimab in subjects with advanced or metastatic solid tumors.

Clinical trials have demonstrated promising efficacy of TIGIT monoclonal antibody in combination with PD-1 monoclonal antibody in immuno-oncology therapy. Cadonilimab simultaneously targets the two well-established immune checkpoints, PD-1 and CTLA-4. Preclinical studies showed that the combination of AK127 and Cadonilimab produced a significantly enhanced anti-tumor effect in mice model.

Based on the promising efficacy seen in both preclinical and clinical studies on TIGIT monoclonal antibody in combination with PD-1 monoclonal antibody therapy, AK127 in combination with Cadonilimab has the potential to demonstrate significant anti-tumor activity in treating patients with solid tumors, further enhance the potential and outlook of combination therapy, and strengthen and enrich the Company’s multi-target portfolio in immuno-oncology therapy.

By developing a rich pipeline of therapeutic antibodies for the treatment of cancer, the Company seeks to transform the treatment paradigm in the immuno-oncology space with combination therapies against various immune targets; and realise the full commercial value of its bi-specific antibodies that are based on a PD-1 antibody backbone. Currently, clinical trials such as Cadonilimab in combination with CD47 monoclonal antibody ( AK117), VEGFR-2 monoclonal antibody (AK109), CD73 monoclonal antibody (AK119) and PD-1/VEGF (AK112) in combination with AK117, have all been successfully initiated.

On October 21, 2021 AskGene, a biotechnology company developing next-generation cytokine therapeutics, and novel bi-specific antibodies to treat cancer and other diseases, and ATUM, a California-based bioengineering company, reported the successful Investigational New Drug (IND) filing in China for AskGene’s new antibody drug (Press release, AskGene Pharmaceuticals, OCT 21, 2021, View Source [SID1234591727]). The antibody was produced using the Leap-In Transposase technology pioneered by ATUM and represents the tenth successful IND clearance globally using this platform.

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"We are encouraged to see how fast the Leap-In Transposase technology has been broadly accepted in the marketplace. We started licensing the platform four years ago and already see the approval of ten successful IND filings," said Oren Beske, Ph.D., Vice President of Business and Strategy at ATUM. "AskGene Pharma was one of the earliest adopters of the Leap-In Transposase technology and we are excited to see how fast they have reached IND filing status."

The Leap-In Transposase technology enables rapid, stable, and robust manufacturing of mammalian cell lines for the production of commercial-grade protein pharmaceuticals. The technology has been evaluated and accepted by multiple independent IND authorizing entities, including the Chinese National Medical Products Administration (NMPA), the European Medicines Agency (EMA), and the U.S. Food and Drug Administration (FDA).

"AskGene is committed to rapidly bringing safe and effective medicines to patients through the use of innovative technologies. We are very pleased to cooperate with ATUM to support us in developing the promising antibodies and next-generation cytokine therapeutics to benefit patients," said AskGene’s CEO, Jeff Lu, Ph.D. "The exceptional genetic stability of the cell lines developed using ATUM’s Leap-in Transposase technology was an important aspect of our successful IND filing and provided an incredibly efficient solution for cell line design and manufacturing."

For more information about the Leap-In Transposase technology, please visit www.atum.bio/pipeline/cld.

On October 21, 2021 Xilio Therapeutics, Inc. (Xilio) a biotechnology company developing tumor-selective immuno-oncology therapies for patients with cancer, reported the pricing of its initial public offering of 7,353,000 shares of its common stock at a price to the public of $16.00 per share (Press release, Xilio Therapeutics, OCT 21, 2021, View Source [SID1234591725]). The gross proceeds to Xilio from the offering, before deducting underwriting discounts and commissions and estimated offering expenses payable by Xilio, are expected to be approximately $117.6 million. In addition, Xilio has granted the underwriters a 30-day option to purchase up to an additional 1,102,950 shares of its common stock at the initial public offering price less underwriting discounts and commissions. All of the shares are being offered by Xilio.

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The shares are expected to begin trading on the Nasdaq Global Select Market under the ticker symbol "XLO" on October 22, 2021. The offering is expected to close on October 26, 2021, subject to the satisfaction of customary closing conditions.

Morgan Stanley, Cowen and Guggenheim Securities are acting as joint book-running managers for the offering. Raymond James is acting as lead manager for the offering.

A registration statement relating to the offering of these securities has been filed with the Securities and Exchange Commission (SEC) and was declared effective on October 21, 2021. The offering is being made only by means of a prospectus. A copy of the final prospectus, when available, may be obtained from Morgan Stanley & Co. LLC by mail at Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, New York 10014, by telephone at (866) 718-1649 or by email at [email protected]; Cowen and Company, LLC by mail at Cowen and Company, LLC, c/o Broadridge Financial Solutions, Attention: Prospectus Department, 1155 Long Island Avenue, Edgewood, New York 11717, by telephone at (833) 297-2926 or by email at [email protected]; and Guggenheim Securities, LLC by mail at Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 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 the 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 jurisdiction.

On October 21, 2021 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that it will host a conference call at 1:30 p.m. PDT/4:30 p.m. EDT on Thursday, Nov. 4, 2021, following the release of its third quarter 2021 financial results (Press release, Puma Biotechnology, OCT 21, 2021, View Source [SID1234591723]).

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The call may be accessed by dialing 1-888-437-3179 (domestic) or 1-862-298-0702 (international). Please dial in at least 10 minutes in advance and inform the operator that you would like to join the "Puma Biotechnology Conference Call." A live webcast of the conference call and presentation slides may be accessed on the Investors section of the Puma Biotechnology website at View Source A replay of the call will be available shortly after completion of the call and will be archived on Puma’s website for 90 days.

On October 21, 2021 Researchers from the University of Dundee and Promega Corporation reported that they have shown how a "three-headed hydra" significantly improves efficacy in targeted protein degradation (Press release, Promega, OCT 21, 2021, View Source [SID1234591720]). This discovery opens new possibilities in a field that is revolutionizing drug discovery for cancer and other targets. The research is published today in Nature Chemical Biology.

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Targeted Protein Degradation

Targeted protein degradation is an area of chemical biology that is revolutionizing drug discovery. It involves co-opting the cell’s natural disposal systems to also remove disease-causing proteins. This system is applicable to diverse therapeutic areas including oncology, inflammation, dermatology, immunology, and respiratory diseases.

Degrading a target protein offers several advantages over traditional inhibitors. This type of drug may show a greater response even at lower doses, and it is more precise with potentially reduced side effects and disease resistance. The first compounds in this class, termed Proteolysis-targeting chimeras (PROTACs), are being trialed as candidate medicines against various cancers and progressing through clinical trials.

PROTACs are conventionally small molecules designed with two heads, called bivalent or heterobifunctional compounds. However, new research carried out by Dundee’s Centre for Targeted Protein Degradation (CeTPD) in collaboration with biotechnology company Promega broke away from this conventional design and showed that degraders can be significantly improved by making them trivalent, i.e. consisting of three heads.

Novel Trivalent PROTACs

The best trivalent PROTAC designed by the researchers proved to be remarkably more potent than their bivalent predecessor compounds, showing in cellular studies stronger anti-cancer activity at a much lower dose and improved pharmacological responses over a wider dose range.

"Three heads can be better than two in PROTACs," says Dr. Alessio Ciulli, Director of the Center for Targeted Protein Degradation. "We hypothesized that we could improve degraders by latching onto the target protein more productively. To do this, we designed trivalent PROTACs by adding an additional protein-binding ligand, in effect creating a three-headed monster that destroys cancer-causing proteins more effectively."

The Dundee/Promega team demonstrated that the new PROTAC works due to the combined effect of two important features of protein and small molecule molecular recognition – avidity and cooperativity. Avidity refers to the combined strength of multiple interactions between two molecules. Cooperativity is a phenomenon shown by molecules with multiple binding sites in which the affinity of the remaining binding sites is increased after a ligand binds to one of them.

The researchers conclude that the trivalent PROTAC concept offers a new strategy that is shown to improve on many aspects of degrader drug action and could in future be applied to a wider range of protein targets, including those thought to be undruggable. If this is shown to be the case, it raises the possibility of scientists being able to develop drugs more easily for diseases for which there are currently no effective treatments, greatly expanding the number of available therapeutics.

"We took a significant risk with this project, but its success has opened new doors for the design of highly potent degraders, as well as other multi-specific compounds," says Dr. Danette Daniels, Senior Research Scientist and Group Leader at Promega Corporation.

Learn More

For more information, read the paper published today in Nature Chemical Biology.

To learn more about Targeted Protein Degradation at Promega, visit www.promega.com/NatureTPD