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FDA Removes Partial Clinical Hold on TakeAim Leukemia Study RP2D Established at 300 mg BID

On July 6, 2023 Curis, Inc., (Nasdaq: CRIS), a biotechnology company focused on the development of emavusertib, an orally available small molecule triple target inhibitor (IRAK4, FLT3 and CLK) for the treatment of hematologic malignancies, reported that the U.S. Food and Drug Administration (FDA) has removed the partial clinical hold on the TakeAim Leukemia Phase 1/2 study of emavusertib (Press release, Curis, JUL 6, 2023, View Source [SID1234633077]). Further, the recommended phase 2 dose (RP2D) for emavusertib as a monotherapy has been established at 300 mg BID in patients with Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndromes (MDS).

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"We are pleased to announce that FDA has removed the partial clinical hold on the TakeAim Leukemia study and that we are proceeding with 300 mg BID as our RP2D. We are working with our clinical sites to enroll targeted patients with AML (patients with a FLT3 or spliceosome mutation who have received ≤ 2 prior lines of treatment). We also plan to initiate a front-line combination study of emavusertib with azacitidine and venetoclax. We believe emavusertib has the potential to be the cornerstone agent in the treatment of hematological malignancies." said James Dentzer, President and Chief Executive Officer of Curis. "In 2024, we expect to have updated data from the TakeAim Leukemia monotherapy study, clarification of a monotherapy registrational study design, and initial data from an azacitidine and venetoclax combination study."

On April 4, 2022, the Company announced that the FDA placed a partial clinical hold on the TakeAim Leukemia study. On August 30, 2022, the Company announced that the FDA notified Curis that it may resume enrollment of additional patients in the monotherapy dose finding phase of the TakeAim Leukemia study, so that the Company could enroll at least nine additional patients at the 200 mg BID dose level. On July 6, 2023, the Company announced the FDA had removed the partial clinical hold on the TakeAim Leukemia study and that the RP2D has been established at 300 mg BID.

In the TakeAim Leukemia study, as of the March 17, 2023 data cutoff for patients dosed prior to February 9, 2023, 84 patients received emavusertib monotherapy, ranging from doses of 200 mg to 500 mg BID. Significant blast count reductions have been observed across all patient groups, regardless of dose level, mutation status, or number of prior lines of treatment. Emerging from these data are two genetically-defined subpopulations of relapsed/refractory (R/R) patients who have demonstrated compelling responses in monotherapy: AML patients with FLT3 mutation and AML patients with spliceosome mutation (U2AF1 or SF3B1 mutation) who have received ≤ 2 prior lines of treatment. In these subpopulations of evaluable patients (patients whose disease has been determined to be evaluable for objective response with baseline and post-treatment marrow assessments) treated with 300 mg BID, 2 of 3 patients with a FLT3 mutation achieved a CR (Complete Response), and 2 of 3 patients with spliceosome mutation achieved a CR or CRh (Complete Response with Partial Hematologic Recovery). The duration of response for these patients ranged from 5.6 to 7.0 months.

"A significant unmet need remains for patients with AML and MDS with the majority of front-line patients relapsing with currently available treatment options," said Dr. Reinhard von Roemeling, Senior Vice President of Clinical Development of Curis. "Emavusertib has the potential to be uniquely positioned as an addition to frontline therapy in combination with standard of care and also as a monotherapy in targeted R/R patient populations."

About emavusertib (CA-4948)

Emavusertib is a triple target inhibitor (IRAK4, FLT3 and CLK). IRAK4 plays an essential role in the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways, which are frequently dysregulated in patients with cancer. TLRs and the IL-1R family signal through the adaptor protein MYD88, which results in the assembly and activation of IRAK4, initiating a signaling cascade that induces cytokine and survival factor expression mediated by the NF-κB protein complex. Preclinical studies targeting IRAK1/4 in combination with FLT3 have demonstrated the ability to overcome the adaptive resistance incurred when targeting FLT3 alone. Further, emavusertib has shown anti-tumor activity across a broad range of hematologic malignancies including monotherapy activity in patient-derived xenografts and synergy with both azacitidine and venetoclax.

About TakeAim Studies

TakeAim Leukemia Study (NCT04278768) – study is open for enrollment.
TakeAim Lymphoma Study (NCT03328078) – study is open for enrollment.

Curis Announces $15.1 Million Registered Direct Offering

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]).

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.

Corvus Pharmaceuticals Announces Publication of Preclinical Data Demonstrating Potential Novel Approach to Immunotherapy Based on Inhibition of ITK with Soquelitinib (CPI-818)

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]).

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.

Caribou Biosciences Announces $25 Million Equity Investment from Pfizer

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).

"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.

BioCryst Reports Inducement Grants Under Nasdaq Listing Rule 5635(c)(4)

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).

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.