Exelixis and Ryvu Therapeutics Establish Exclusive License Agreement to Develop Novel STING Agonist-Based Targeted Cancer Therapies

O July 7, 2022 Exelixis, Inc. (Nasdaq: EXEL) and Ryvu Therapeutics S.A. ("Ryvu") (Warsaw Stock Exchange: RVU) reported that the companies have entered into an exclusive license agreement focused on the development of novel targeted therapies utilizing Ryvu’s STING (STimulator of INterferon Genes) technology (Press release, Exelixis, JUL 7, 2022, View Source [SID1234616518]). The agreement expands Exelixis’ portfolio of biotherapeutics by combining Ryvu’s proprietary small molecule STING agonists and STING biology know-how with Exelixis’ network of expertise and resources in antibody engineering, antibody-drug conjugate (ADC) technologies, and proven history of developing and commercializing oncology therapeutics.

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"Ryvu has leveraged its in-depth structural protein knowledge to rationally design small molecules that are structurally distinct from known STING agonists and outperform most other potentially competitive compounds in in vitro immune cell assays"

Under the terms of the agreement, Exelixis will pay Ryvu an upfront fee of $3 million in exchange for certain rights to Ryvu’s STING agonist small molecules, which Exelixis will seek to incorporate into targeted therapies such as ADCs. Exelixis will lead all research activities and, upon selection of each development candidate, will be responsible for all development and commercialization activities. Ryvu will provide expert guidance and know-how during the early research phase of the partnership, and will be eligible to receive development, regulatory and commercialization milestone payments, as well as tiered royalties on the annual net sales of any products that are successfully commercialized under the collaboration. Ryvu will also retain all development and commercial rights to develop its STING agonist portfolio as standalone small molecules.

"Gaining access to novel targets and technologies is an essential component of our strategy to expand our biotherapeutics pipeline, and this relationship allows Exelixis to capitalize on Ryvu’s STING-related assets and expertise," said Peter Lamb, Ph.D., Executive Vice President, Scientific Strategy and Chief Scientific Officer, Exelixis. "Ryvu’s portfolio of STING agonists comprises compounds with diverse drug-like attributes that have been extensively characterized. This includes small molecule agonists with demonstrated activity against all STING variants that are suitable for incorporation into ADCs. We believe that these properties will support the development of novel, STING-targeted therapies with the potential to provide benefit to more patients across diverse cancer indications, which is a critical priority for everyone at Exelixis."

The STING pathway can be activated in immune cells in the tumor microenvironment and in tumor cells, and induces innate and adaptive immunity via activation of antigen presenting cells (APCs), cytotoxic T cells and natural killer (NK) cells. Targeted delivery of Ryvu’s STING agonist payloads could provide a differentiated and novel mechanism of action for killing cancer cells. Ryvu’s STING agonists have been rationally designed for differentiation from competitor compounds and have demonstrated STING-dependent, durable anti-tumor activity and cytokine release in preclinical models.

"Ryvu has leveraged its in-depth structural protein knowledge to rationally design small molecules that are structurally distinct from known STING agonists and outperform most other potentially competitive compounds in in vitro immune cell assays," said Krzysztof Brzózka, Ph.D., Chief Scientific Officer, Ryvu. "Exelixis’ expertise in the development of targeted cancer therapies and its growing network of biologics resources and assets make it the partner of choice for realizing the potential of our STING technology as the foundation for novel cancer therapies and provides another strong validation for our immune-oncology acumen and Ryvu discovery platform. We are excited to partner with a leading oncology company that shares our passion for innovation, strives toward achieving a meaningful impact on patient care, and advances the boundaries of oncology therapeutics development."

InnoCare Announces Approval of Clinical Trial of Novel Targeted Protein Degrader ICP-490 in China

On July 7, 2022 InnoCare Pharma (HKEX: 09969), a leading biopharmaceutical company focusing on the treatment of cancer and autoimmune diseases, reported that the company has received Investigational New Drug (IND) approval of clinical trial from the NMPA (National Medical Products Administration) for its novel targeted protein degrader ICP-490 for the treatment of multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL) (Press release, InnoCare Pharma, JUL 7, 2022, View Source [SID1234616517]).

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ICP-490 is developed from InnoCare’s molecular glue platform. By specifically binding to CRL4-CRBN-E3 ligase complex, ICP-490 induces ubiquitination and degradation of transcription factors including Ikaros and Aiolos, thereby downregulating the expression of IRF4, an oncogenic transcription factor that drives multiple myeloma to exert direct anti-myeloma effects. It also has immunomodulatory effects by enhancing the function of effector T cells, resulting from Ikaros and Aiolos degradation and the degradation-mediated releasing of interleukin IL-2.

Multiple myeloma (MM) is a malignant tumor with clonal abnormal proliferation of plasma cells, which is characterized by abnormal proliferation of bone marrow plasma cells and most of them with overproduction of monoclonal immunoglobulin (M protein). MM is often accompanied by multiple osteolytic lesions, hypercalcemia, anemia, kidney injury, etc. MM accounts for about one percent of tumor diseases and 10 percent of blood tumors1.

Non-Hodgkin’s lymphoma (NHL) is the most common hematological malignancy in the world, accounting for nearly three percent of cancer diagnosis and death2. NHL ranks among the top 10 common malignant tumors in China. Its common types include diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).

Dr. Jasmine Cui, the co-founder, Chairwoman and CEO of InnoCare said, "InnoCare has built a strong pipeline in the field of blood tumor. With the approval of ICP-490 for clinical trials, InnoCare will further strengthen its blood tumor pipeline and aim to provide better treatment options for those patients in China and around the world."

Disruptive Pharma raises 41 million SEK to develop pipeline project towards clinical stage

On July 6, 2022 Disruptive Pharma reported the company closed a 41 million SEK financing round (Press release, Disruptive Pharma, JUL 6, 2022, View Source [SID1234649942]). We couldn’t be more excited as it allows us to fund continued development of lead pipeline project towards clinical proof-of-concept. The investment also enables Disruptive Pharma to fund continued development towards identification of a lead candidate and to complete the development of oral grade Pharma MMC. Pharmaceutical grade mesoporous magnesium carbonate, Pharma MMC, is an innovative drug delivery technology for amorphous stabilization and solubility enhancement of drug substances and for unique drug formulations. Much appreciation to our shareholders who continue to support and invest in us! We are also delighted to welcome our new shareholders who believe in our mission.

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ReCode Therapeutics to Participate in Upcoming July Investor Conferences?

On July 6, 2022 ReCode Therapeutics, a genetic medicines company using superior delivery to power the next wave of mRNA and gene correction therapeutics, reported that Company leadership will participate in two upcoming investor conferences in July (Press release, ReCode Therapeutics, JUL 6, 2022, View Source;utm_medium=rss&utm_campaign=recode-therapeutics-to-participate-in-upcoming-july-investor-conferences [SID1234619534]):

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William Blair Biotech Focus Conference (New York, NY)
Format: Panel Presentation
Date: Wednesday, July 13, 2022
Time: 2:00 – 2:45 p.m. ET
Cowen RNA Therapeutics Summit (Virtual)
Format: Panel Presentation
Date: Thursday, July 21, 2022
Time: 12:55 – 1:40 p.m. ET

Avalo Therapeutics Announces One-for-Twelve Reverse Stock Split

On July 6, 2022 Avalo Therapeutics, Inc. (Nasdaq: AVTX) reported a one-for-twelve reverse stock split of the Company’s common stock, par value $0.001, which will be effective at 5:00 pm Eastern Time tomorrow, July 7, 2022 (Press release, Avalo Therapeutics, JUL 6, 2022, View Source [SID1234616533]). The Company’s common stock will trade on the Nasdaq Capital Market on a split-adjusted basis beginning on July 8, 2022, under the Company’s existing trading symbol "AVTX".

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The Company is implementing the reverse stock split as planned to increase the per share price of its common stock to regain compliance with the listing requirements of the Nasdaq Capital Market. The new CUSIP number following the reverse stock split will be 05338F207.

The reverse stock split will affect all stockholders uniformly and will not alter any stockholder’s percentage ownership interest in the Company, except to the extent that the reverse stock split results in any of the Company’s stockholders owning a fractional share as described below.

The reverse stock split will reduce the number of shares of common stock issued and outstanding from approximately 112,868,677 to approximately 9,405,724. No fractional shares will be issued in connection with the reverse stock split. Each stockholder who would otherwise be entitled to receive a fraction of a share of the Company’s common stock will instead receive one whole share of common stock.

As of the effective date of the reverse stock split, the number of shares of common stock available for issuance under the Company’s equity incentive plans and issuable upon the exercise of stock options and warrants outstanding immediately prior to the reverse stock split will be proportionately affected by the reverse stock split. The exercise prices of the Company’s outstanding options and warrants will be adjusted in accordance with their respective terms.

There will be no change to the number of authorized shares or the par value per share.

American Stock Transfer & Trust Company, LLC ("AST") is acting as the exchange agent for the reverse stock split and will provide instructions to stockholders of record regarding the reverse stock split. AST will be issuing, automatically and without the need for stockholder action, all of the post-split shares in paperless, "book-entry" form, and AST will hold the shares in an account set up for the stockholder. Stockholders who currently hold certificates need not exchange their certificates to receive their "book-entry" accounts at AST; those current certificates do not need to be submitted to AST for exchange in order to receive the "book-entry" accounts. Those stockholders holding common stock in "street name" will receive instructions from their brokers.