On July 12, 2021 IDEAYA Biosciences, Inc. (Nasdaq:IDYA) reported the closing of its underwritten public offering of 5,333,333 shares of its common stock at a public offering price of $17.25 per share, before underwriting discounts and commissions, including the exercise in full by the underwriters of their option to purchase up to an additional 695,652 shares of common stock in the offering (Press release, Ideaya Biosciences, JUL 12, 2021, View Source [SID1234584791]). The net proceeds from the offering were approximately $86.1 million, after deducting the underwriting discount and commissions and estimated offering expenses payable by IDEAYA. All shares in the offering were offered by IDEAYA.

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IDEAYA intends to use the net proceeds of the offering, along with its existing cash, cash equivalents and short-term and long-term marketable securities to fund (i) clinical development of IDE397, its MAT2A inhibitor development candidate, (ii) preclinical and clinical development of other product candidates in its research pipeline targeting poly (ADP-ribose) glycohydrolase, or PARG, a MTAP synthetic lethality target (other than MAT2A), and DNA damage targets, as well as its share of costs for targeting WRN under IDEAYA’s Collaboration, Option and License Agreement with GSK, (iii) ongoing early clinical development of darovasertib (IDE196), its PKC inhibitor, in metastatic uveal melanoma, or MUM, and other solid tumors having GNAQ/11 hotspot mutations, including as monotherapy and as combination therapies with binimetinib, a MEK inhibitor, and independently with crizotinib, in each case pursuant to a clinical trial and drug supply agreement with Pfizer, (iv) synthetic lethality target and biomarker research and development activities and (v) working capital and other general corporate purposes.

J.P. Morgan, Citigroup, Jefferies and Guggenheim Securities acted as joint book-running managers for the offering.

The public offering was made by IDEAYA pursuant to a shelf registration statement on Form S-3 that was previously filed with and declared effective by the U.S. Securities and Exchange Commission, or the SEC. The offering was made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. A final prospectus supplement and accompanying prospectus relating to the offering has been filed with the SEC and is available on the SEC’s website at View Source Copies of the final prospectus supplement and the accompanying prospectus relating to the offering may also be obtained by request from: J.P. Morgan, by mail at 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]; Citigroup, by mail at Citigroup Global Markets Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at 1-800-831-9146; Jefferies, by mail at Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, or by telephone at 877-547-6340 or 877-821-7388, or by email at [email protected]; or Guggenheim Securities, by mail at Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, New York, NY 10017, or by telephone at (212) 518-5548 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.

On July 12, 2021 Akeso, Inc. reported that, CD47 monoclonal antibody (AK117), a second-generation novel drug for immuno-oncology therapy independently developed by the Company, has completed phase I dose escalation trial in Australia (Press release, Akeso Biopharma, JUL 12, 2021, View Source [SID1234584790]). AK117 resulted in no dose-limiting toxicity (DLT) and no anemia of clinical significance in subjects in all dose escalation cohorts (with 0.3 mg/kg to 45 mg/kg administered once-weekly (QW)), and was well tolerated by subjects in all cohorts. Low-dose priming was not required.

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Akeso has obtained approval from the National Medical Products Administration (NMPA) of China to initiate phase Ib/II clinical trial of AK117 in combination with azacitidine for the treatment of acute myeloid leukemia (AML). AK117, a second-generation CD47 monoclonal antibody, has a significantly improved safety profile compared to the first-generation CD47 monoclonal antibody, and AK117 in combination with azacitidine is expected to perform better than similar drugs in the treatment of AML. Previous studies of AK117 in myelodysplastic syndromes (MDS) have shown its advantages of safety and the majority of MDS patients had hematologic improvement while receiving AK117 treatment. To date, clinical trials of AK117 in both solid tumors and hematologic tumors have been initiated and began patient dosing.

AML is a group of highly heterogeneous diseases with clonal proliferation abnormalities of hematopoietic stem cells and is the most common type of adult acute leukemia. CD47 is highly expressed on the surface of several tumor cells, including solid tumors and hematologic tumors, and is associated with poor prognosis. CD47 blockade stimulates phagocytosis of tumor cells by macrophages and promotes adaptive immune response. Preclinical data showed that CD47 monoclonal antibody in combination with azacitidine can further induce endogenous expression of calreticulin on the cell surface, thereby further enhancing the phagocytosis of tumors by macrophages. At the same time, there are clinical data showing that CD47 monoclonal antibody in combination with azacitidine is significantly more effective than azacitidine alone in treating AML subjects who are not suitable for chemotherapy at first treatment, and is safe and well tolerated.

Information about AK117 (CD47 Monoclonal Antibody)

AK117 is a novel humanized IgG4 mAb independently developed by the Company. It can bind with CD47 expressed on tumor cells to prevent the interaction between CD47 and its receptor, SIRPα, expressed on macrophages so as to enhance phagocytosis to inhibit the growth of tumor cells. Previously published data demonstrated exceptional safety profile. AK117 resulted in no DLT and no anemia of clinical significance in subjects in all doseescalation cohort (the highest dose cohort was 45 mg/kg QW), and was well tolerated by subjects in all cohorts. The CD47 receptor occupancy rate (RO) of the peripheral blood T cells has reached and maintained at 100% in the 3 mg/kg cohort.

On July 12, 2021 Tempus, a leader in artificial intelligence and precision medicine, reported results from validation studies demonstrating the reliable analytical performance of the Tempus|xF liquid biopsy (Press release, Tempus, JUL 12, 2021, View Source [SID1234584789]). When validated against methods such as ddPCR, the Roche AVENIO kit, and the Tempus|xT solid tumor assay, xF demonstrated high sensitivity and specificity for calling SNVs, indels, CNVs, and gene rearrangements, making the liquid biopsy next-generation sequencing assay a preferred sequencing option should tumor tissue not be available.

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xF is Tempus’ non-invasive, 105-gene liquid biopsy panel focused on oncogenic and resistance mutations in cell-free DNA. Designed to provide clinical decision support for solid tumors, xF is an alternative to tissue-based biopsies in identifying biomarkers, detecting resistant mutations, monitoring response to treatment or disease progression, and spotting early recurrence in real time. npj Precision Oncology published xF’s analytical validation, highlighting the assay’s high sensitivity and specificity for detecting single-nucleotide variants, insertions/deletions, copy number variants, and gene rearrangements. The validation results show high accuracy in detecting clinically-actionable targets compared to orthogonal testing methods.

"This study underscores the clinical value of liquid biopsies, a non-invasive sequencing option and another powerful tool for oncologists to determine clinically-actionable alterations necessary for highly-effective and personalized treatment options," said Dr. Kimberly Blackwell, Chief Medical Officer at Tempus. "At Tempus, we have also found that xF is especially beneficial when used in combination with standard tissue sequencing for patients with advanced cancer, and therefore it is important to offer oncologists both a liquid biopsy and solid tumor assay on a single platform."

xF is part of Tempus’ library of assays conducted in its CLIA-certified and CAP-accredited laboratory, which also includes xE, an assay that analyzes the whole exome and xT, an assay that analyzes 648 genes in solid tumor and hematologic malignancies.

On July 12, 2021 Caribou Biosciences, Inc., a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported that the first patient has been dosed in its open-label, multicenter ANTLER phase 1 clinical trial (NCT04637763) to evaluate the company’s lead product candidate, CB-010, in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) (Press release, Caribou Biosciences, JUL 12, 2021, View Source [SID1234584788]). CB-010 is an allogeneic anti-CD19 CAR-T cell therapy derived from healthy donor T cells that have been engineered using Caribou’s chRDNA technology to reduce the risk of graft versus host disease (GvHD) and knock out PD-1 to boost the persistence of CAR-T cell antitumor activity.

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"Advancing our first allogeneic CAR-T cell therapy into the clinic represents a major milestone for Caribou," said Rachel Haurwitz, Ph.D., Caribou’s president and chief executive officer. "Using our proprietary chRDNA CRISPR technology, we have developed a pipeline of off-the-shelf CAR-T and CAR-NK cell therapies with the potential to serve a greater number of patients than autologous approaches. We believe that improving cell persistence is the key to unlocking the full potential of these therapies. Using our technologies, we edit the genome of healthy donor-derived T cells to enable highly specific and efficient insertion or deletion of genes at multiple sites. This allows us to create sophisticated allogeneic cell therapies with enhanced characteristics to potentially improve their effectiveness and durability of antitumor activity compared to other allogeneic cell therapies. With CB-010, we are evaluating the potential persistence-enhancing effects of removing the PD-1 protein from the surface of these CD19-targeted CAR-T cells."

Cherry Thomas, M.D., senior vice president of clinical development, added, "We are thrilled to advance CB-010 in the clinic and believe it potentially represents a promising, differentiated therapy for patients. Initially, we will evaluate escalating doses of CB-010 in relapsed or refractory B cell non-Hodgkin lymphoma patients with the goals of assessing safety and tolerability and to establish a dose level for the expansion phase of the study. We look forward to having initial clinical data from this clinical trial in 2022."

About CB-010

CB-010 is an allogeneic anti-CD19 CAR-T cell therapy derived from healthy donor T cells. The cells are engineered using Caribou’s chRDNA CRISPR technology to integrate a CD19-CAR site-specifically into the T cell genome at the site of the TRAC gene locus, thus eliminating expression of the T cell receptor to reduce the risk of GvHD. The cells are modified further using chRDNA to knock out the gene encoding PD-1, thus preventing the expression of the PD-1 protein on the CAR-T cell surface. Elimination of PD-1 expression is designed to boost the persistence of CAR-T cell antitumor activity by reducing CB-010 exhaustion and thereby potentially providing a better therapeutic index compared to other allogeneic CAR-T cells. An additional step in the manufacturing process for CB-010 is designed to remove residual T cells expressing a T cell receptor, further reducing the risk of GvHD.

About the Phase 1, Dose Escalation Study of CB-010 (ANTLER Study, NCT04637763)

The ANTLER study is an open-label, multicenter phase 1 clinical trial designed to evaluate CB-010 in adults with r/r B-NHL. In the dose-escalation part of the study, adults who have failed at least two lines of chemo and/or immunotherapy will receive CB-010 following lymphodepletion. In a standard 3+3 dose escalation design, increasing doses of CB-010 will be evaluated to determine safety and tolerability and to establish a dose level for the expansion part of the study. The primary objective of the dose escalation is to evaluate the safety and tolerability of CB-010 and the primary objective of the expansion part of the study is to evaluate the efficacy of CB-010 in a defined population. Patients who have received a prior CD19-targeted therapy will be excluded from the study.

About Caribou’s Novel Next-Generation CRISPR Platform

CRISPR genome editing uses easily designed, modular biological tools to make DNA changes in living cells. There are two basic components of Type II CRISPR systems: the nuclease protein that cuts DNA and the RNA molecule(s) that guide the nuclease to generate a site-specific, double-stranded break, leading to an edit at the targeted genomic site. CRISPR systems occasionally edit unintended genomic sites, known as off-target editing, which may lead to harmful effects on cellular function and phenotype. In response to this challenge, Caribou has developed chRDNAs (pronounced "chardonnays"), RNA-DNA hybrid guides that direct substantially more precise genome editing compared to all-RNA guides. Caribou is deploying the power of the chRDNA technology to carry out high efficiency multiple edits, including multiplex gene insertions, to develop CRISPR-edited therapies.

On July 12, 2021 OPKO Health, Inc. (NASDAQ: OPK) reported it has entered into an exclusive worldwide agreement with privately held CAMP4 Therapeutics Corporation (CAMP4) for the development, manufacture and commercialization of therapeutics utilizing the AntagoNAT technology, an oligonucleotide platform developed under OPKO CURNA (Press release, Opko Health, JUL 12, 2021, View Source [SID1234584787]). AntagoNATs are oligonucleotide compounds that target non-coding natural antisense transcripts leading to an upregulation of a desired functional protein. CAMP4 has prioritized OPKO’s lead AntagoNAT compound to progress into clinical trials for the treatment of Dravet syndrome.

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Under the terms of the agreement, OPKO will receive an upfront payment and shares of CAMP4. In addition, OPKO will be eligible to receive up to $93.5 million and additional shares upon the achievement of certain development and sales milestones for products developed from this technology and associated intellectual property. CAMP4 will also pay OPKO double-digit royalties on product sales.

"We are delighted to enter into this licensing agreement to accelerate the development and commercialization of potential disease-modifying therapeutics. With a clear focus on therapeutics that restore healthy gene expression, CAMP4 has the expertise to advance our Dravet syndrome compound through the necessary patient trials. This agreement validates our technology and allows OPKO to focus resources on other areas of our business. We continue to seek license opportunities to monetize and leverage our early-stage assets," said Phillip Frost, M.D., Chairman and Chief Executive Officer of OPKO.

According to the Epilepsy Foundation, Dravet syndrome is a rare, drug-resistant epilepsy that begins in the first year of life in an otherwise healthy infant. It is estimated that 1-in-20,000 to 1-in-40,000 individuals have Dravet syndrome. Most cases are due to SCN1A gene mutations and most children develop varying degrees of neurodevelopmental disability.

CAMP4 is pioneering a novel approach to programmable therapeutics that combines a deep understanding of regulatory RNA and gene expression with a complementary and customizable oligonucleotide modality. The company’s RNA Actuating Platform’s proprietary insights enable drug discovery and development that aims to harness the power of RNA to upregulate the expression of genes and unlock the potential to create treatments for hundreds of diseases affecting millions of patients.