On July 6, 2023 Curis, Inc. (Nasdaq: CRIS), a biotechnology company focused on the development of emavusertib, a triple target inhibitor (IRAK4, FLT3 and CLK) for the treatment of hematologic malignancies, reported that it has entered into definitive agreements led by existing investors for the purchase of 18.4 million of its shares of common stock at a purchase price of $0.82 per share in a registered direct offering priced at-the-market under Nasdaq rules (Press release, Curis, JUL 6, 2023, View Source [SID1234633076]).

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Gross proceeds to the Company from the offering are expected to be approximately $15.1 million, before deducting the placement agents’ fees and other offering expenses payable by Curis. Curis intends to use the net proceeds from the offering on research, development, working capital, and other general corporate purposes. The closing of the offering is expected to occur on or about July 10, 2023, subject to the satisfaction of customary closing conditions. Cantor Fitzgerald & Co. and Truist Securities, Inc. are acting as the placement agents for the offering.

The shares are being offered pursuant to a shelf registration statement on Form S-3 (File No. 333-254362) that was filed with the United States Securities and Exchange Commission ("SEC") on March 16, 2021, as amended by Post-Effective Amendment No. 1 to Form S-3 Registration Statement and Post-Effective Amendment No. 2 to Form S-3 Registration Statement, each filed with the SEC on February 24, 2022. A prospectus supplement relating to and describing the terms of the offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. The offering is being made only by means of a prospectus and related prospectus supplement. When available, electronic copies of the prospectus supplement and the accompanying prospectus may also be obtained from Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Avenue, 4th Floor, New York, NY, 10022, by email at [email protected] or from Truist Securities, Inc., Attention: Prospectus Department, 3333 Peachtree Road NE, 9th floor, Atlanta, Georgia 30326, by telephone at (800) 685-4786, 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 other jurisdiction.

On July 6, 2023 Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported the publication of preclinical data on soquelitinib (formerly known as CPI-818), the Company’s ITK inhibitor product candidate, which highlighted the selective inhibition of ITK to potentially enhance anti-tumor immune response to hematologic and solid tumors and provide a novel approach to cancer immunotherapy (Press release, Corvus Pharmaceuticals, JUL 6, 2023, View Source [SID1234633075]).

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The publication, entitled "Selective Inhibition of Interleukin 2 Inducible T Cell Kinase (ITK) Enhances Anti-Tumor Immunity in Association with Th1-skewing, Cytotoxic T cell Activation, and Reduced T Cell Exhaustion," provides a detailed overview of the chemical structure, enzymatic activity and immunobiologic properties of soquelitinib. The published research was a result of collaborations between scientists at Corvus and researchers at the University of Michigan, The Ohio State University, Peking University and Stanford University. The publication is now available online as a preprint at bioRxiv.org and on the Publications and Presentations page of the Corvus website.

"This significant scientific report demonstrates the potential of highly selective ITK inhibition, now enabled by soquelitinib. The data indicate that this mechanism, if approved, may become the backbone of a new immunotherapy approach to cancer and we believe it will extend the opportunity for the continued development of soquelitinib as a single agent or in combination with other therapies to treat a variety of cancer tumor types," said Richard A. Miller., co-founder, president and chief executive officer of Corvus.

The findings reported indicate that ITK is a novel drug target and its blockade may enhance the body’s immune response to cancer. ITK is an enzyme predominantly expressed by T lymphocytes. ITK plays a major role in the function of T cells which are generally acknowledged as a critical cell in the immunotherapy of cancer. Soquelitinib is currently being studied in a Phase 1/1b clinical trial as a single agent therapy in patients with relapsed T cell lymphoma (TCL). Corvus plans to meet with the FDA in the third quarter of 2023 to discuss a Phase 3 registration clinical trial in patients with relapsed TCL.

Key results from the preclinical studies described in the publication demonstrated that soquelitinib:

Is a covalent, irreversible inhibitor that selectively binds to and inhibits ITK function while sparing other closely related kinases, including resting lymphocyte kinase (RLK).
Inhibited Th2 T cell function and the production of various Th2 cytokines leading to Th1 skewing and production of interferon gamma and tumor necrosis factor, which are important cytokines in tumor rejection. Th2 cytokines have been previously implicated in promoting tumor growth and are also involved in autoimmune and allergic diseases.
Activated cytotoxic killer cells and increases infiltration of these cells into tumors.
Reduced and reversed T cell exhaustion resulting in a more potent and prolonged immune response. T cell exhaustion is often a major reason for resistance to immune checkpoint therapy.
Led to in vivo anti-tumor activity in several mouse tumor models, including colon, renal, melanoma, B cell and T cell tumors.

On July 6, 2023 Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported that Pfizer Inc. (NYSE: PFE) has made a $25 million equity investment in the company (Press release, Caribou Biosciences, JUL 6, 2023, View Source [SID1234633074]). Pfizer purchased 4,690,431 of Caribou common shares at a price of $5.33 per share, pursuant to the terms of a Securities Purchase Agreement dated June 29, 2023. The purchase by Pfizer closed on June 30, 2023. In conjunction with the investment, Dr. Krishnaswami has joined Caribou’s Scientific Advisory Board (View Source).

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"We believe Pfizer’s investment in Caribou highlights the potential of our clinical programs and we are excited to establish this partnership with one of the world’s premier biopharmaceutical companies," said Rachel Haurwitz, PhD, Caribou’s president and chief executive officer. "We are actively advancing our allogeneic CAR-T cell therapy pipeline and look forward to providing updates from all of our programs over the next six months, including 6-month dose escalation data from our ANTLER Phase 1 clinical trial for CB-010, dose escalation updates on our CaMMouflage Phase 1 clinical trial for CB-011, and submission of an investigational new drug application for CB-012."

"We are encouraged by Caribou’s chRDNA genome-editing technology and the potential of allogeneic cell therapies as a promising off-the-shelf approach to cancer treatment," said Dr. Krishnaswami. "Pfizer has a long history of supporting early, innovative science in the biotech ecosystem, and we look forward to supporting Caribou as they continue to advance their ANTLER Phase 1 trial for CB-010, as well as their clinical program for CB-011, an allogeneic anti-BCMA cell therapy for multiple myeloma."

Caribou will use the proceeds of this investment to advance CB-011, an immune cloaked allogeneic CAR-T cell therapy currently being evaluated in the CaMMouflage Phase 1 clinical trial in patients with relapsed or refractory multiple myeloma (r/r MM). Caribou will maintain full ownership and control of its pipeline of allogeneic CAR-T and CAR-NK cell therapies.

The securities sold in this financing were made in a transaction not involving a public offering and have not been registered under the Securities Act of 1933, as amended, and may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements. This press release shall not constitute an offer to sell or the solicitation of an offer to buy the common shares, nor shall there be any sale of the common shares 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.

About CB-010
CB-010 is the lead product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL). In the ongoing ANTLER Phase 1 trial, Caribou is enrolling second-line patients with large B cell lymphoma (LBCL) comprising four different subtypes of aggressive r/r B-NHL (DLBCL NOS, PMBCL, HGBL, and tFL). CB-010 is an allogeneic anti-CD19 CAR-T cell therapy engineered using Cas9 CRISPR hybrid RNA-DNA (chRDNA) technology. CB-010 is the first allogeneic CAR-T cell therapy in the clinic, to Caribou’s knowledge, with a PD-1 knockout, a genome-editing strategy designed to improve antitumor activity by limiting premature CAR-T cell exhaustion. To Caribou’s knowledge, CB-010 is also the first anti-CD19 allogeneic CAR-T cell therapy to be evaluated in the second-line setting and has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, and Orphan Drug designations by the FDA. Additional information on the ANTLER trial (NCT04637763) can be found at clinicaltrials.gov.

About CB-011
CB-011 is the second product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in patients with relapsed or refractory multiple myeloma (r/r MM) in the CaMMouflage Phase 1 trial. CB-011 is an allogeneic anti-BCMA CAR-T cell therapy engineered using Cas12a chRDNA technology. To Caribou’s knowledge, CB-011 is the first allogeneic CAR-T cell therapy in the clinic that is engineered to improve antitumor activity through an immune cloaking strategy with a B2M knockout and insertion of a B2M–HLA-E fusion protein to blunt immune-mediated rejection. CB-011 has been granted Fast Track designation by the FDA. Additional information on the CaMMouflage trial (NCT05722418) can be found at clinicaltrials.gov.

About CB-012
CB-012 is the third product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in investigational new drug (IND)-enabling studies. To Caribou’s knowledge, CB-012 is the first allogeneic CAR-T cell therapy with both checkpoint disruption, through a PD-1 knockout, and immune cloaking, through a B2M knockout and B2M–HLA-E fusion protein insertion; both armoring strategies are designed to improve antitumor activity. CB-012 is engineered with five genome edits, enabled by Caribou’s patented next-generation CRISPR technology platform, which uses Cas12a chRDNA genome editing to significantly improve the specificity of genome edits.

On July 6, 2023 BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) reported that the compensation committee of BioCryst’s board of directors granted 13 newly-hired employees stock options to purchase an aggregate of 99,200 shares, and restricted stock units (RSUs) covering an aggregate of 51,650 shares, of BioCryst common stock (Press release, BioCryst Pharmaceuticals, JUL 6, 2023, View Source [SID1234633073]). The options and RSUs were granted as of June 30, 2023, as inducements material to each employee entering into employment with BioCryst. The options and RSUs were granted in accordance with Nasdaq Listing Rule 5635(c)(4).

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The options have an exercise price of $7.04 per share, which is equal to the closing price of BioCryst common stock on the grant date. The options and RSUs vest in four equal annual installments beginning on the one-year anniversary of the grant date, in each case subject to the new employee’s continued service with the company. Each stock option has a 10-year term. The options and RSUs are subject to the terms and conditions of BioCryst’s Inducement Equity Incentive Plan and a stock option agreement or restricted stock unit agreement, as applicable, covering the grant.

On July 6, 2023 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported a publication in Nature Medicine1 entitled: ‘Transcriptional hallmarks of persisting CD19 CAR T-cells in children with leukaemia,’ describing new findings from the original Obecabtagene autoleucel (obe-cel) study (CARPALL2) in Pediatric B-cell Acute Lymphoblastic Leukemia (Press release, Autolus, JUL 6, 2023, View Source [SID1234633070]).

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Long-term CAR T cell persistence is associated with durable responses in some cancers, including B-cell acute lymphoblastic leukemia (B-ALL). Obe-cel, Autolus’ CD19 CAR, was designed to maximize CAR T cell persistence by tuning the affinity to CD19 to result in more physiological signaling.

The transcriptional mechanisms behind long-term persistence of antigen-specific T cells are not fully understood. The long-term persistence of obe-cel CAR T cells in patients allows their isolation by flow-cytometric sorting from peripheral blood at very late time-points (including several years) after infusion. This has enabled researchers at University College London, working in collaboration with the Wellcome Sanger Institute, to perform detailed single-cell analysis on long-term persisting CAR T cells from patients treated in the CARPALL study2, the first clinical study of obe-cel in pediatric B-ALL.

Publishing her findings in Nature Medicine today, Dr Sara Ghorashian described how long-term persistence was associated with a particular T cell population which was CD4/CD8 double-negative, but expressed the transcription factor TOX and Granzyme K. This phenotype emerged across all clones and subsets of T-cells, suggesting that CAR T-cells converge transcriptionally to this state to maintain persistence. This finding fits with the newly described TPEX sub-population found in chronic viral infections.

"Long-term CAR T cell persistence is required for durable responses in B-ALL but is not well understood," said Dr Martin Pule, Chief Scientific Officer and Founder of Autolus: "Dr Ghorashian has exploited the ability to isolate obe-cel CAR T-cells from patients at late time-points to further our understanding of which transcriptional states drive long-term persistence. These findings will allow us to work towards further refining CAR T manufacturing to favor these transcriptional states."