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."

On July 6, 2023 Allarity Therapeutics, Inc. (Nasdaq: ALLR) ("Allarity" or the "Company"), a clinical-stage pharmaceutical company developing novel oncology therapeutics together with drug-specific DRP companion diagnostics for personalized cancer care, reported the pricing of its "reasonable best efforts" public offering of 2,444,445 shares of common stock (or common stock equivalents in lieu thereof) and common warrants to purchase up to 2,444,445 shares of common stock at an effective combined price of $4.50 per share and common warrant for aggregate gross proceeds of approximately $11 million, before deducting placement agent fees and other offering expenses (Press release, Allarity Therapeutics, JUL 6, 2023, View Source [SID1234633062]). The warrants will have an exercise price of $4.50 per share, will be exercisable immediately and will expire five years from the initial exercise date.

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The closing of the offering is expected to occur on or about July 10, 2023, subject to the satisfaction of customary closing conditions. The Company intends to use a portion of the net proceeds of this offering to pay account payables and accrued liabilities outstanding, to make payments under certain license agreements, to pay off a certain outstanding promissory note, to conduct clinical trials, to redeem a portion of its Series A Convertible Preferred Stock and for working capital and general corporate purposes. In connection with the offering, the Company has agreed to reduce the exercise price of the outstanding warrants issued in the April 2023 offering to purchase up to 250,000 shares of common stock from $34.00 per share to $4.50 per share and extend the termination date from April 21, 2028 to July 10, 2028, effective upon the closing of this offering.

A.G.P./Alliance Global Partners is acting as sole placement agent for the offering.

The securities described above are being offered pursuant to a registration statement on Form S-1 (File No. 333-272469) previously filed with the Securities and Exchange Commission (SEC) which became effective on July 5, 2023. The offering is being made only by means of a prospectus forming part of the effective registration statement. Copies of the preliminary prospectus and, when available, copies of the final prospectus, relating to the offering may be obtained on the SEC’s website located at View Source Electronic copies of the final prospectus relating to the offering may be obtained, when available, from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022, or by telephone at (212) 624-2060, 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 Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") reported that the U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review for the company’s Biologics License Application (BLA) for zolbetuximab, a first-in-class investigational Claudin 18.2 (CLDN18.2)-targeted monoclonal antibody, for first-line treatment of patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are CLDN18.2-positive (Press release, Astellas, JUL 6, 2023, View Source [SID1234633047]). If approved, zolbetuximab would be the first CLDN18.2-targeted therapy available in the U.S. for these patients.

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Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of January 12, 2024. The FDA reviewed the application under its Real-Time Oncology Review (RTOR) program, which aims to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible.

In the U.S., it is estimated that 26,500 people will be diagnosed with gastric cancer and 11,130 will die from the disease in 2023.1 Early-stage gastric cancer symptoms frequently overlap with more common stomach-related conditions, often resulting in gastric cancer diagnosis in the advanced or metastatic stage, or once it has spread from the tumor’s origin to other body tissues or organs.2 The five-year relative survival rate for patients at the metastatic stage is 6.6%.1

"Astellas is committed to bringing innovative therapies to patients with hard-to-treat cancers, including gastric cancer. While rare in the U.S., gastric cancer can be deadly when diagnosed in the late stages," said Moitreyee Chatterjee-Kishore, PhD, MBA, Senior Vice President and Head of Immuno-Oncology Development, Astellas. "The FDA’s acceptance of the Biologics License Application filing and Priority Review designation for zolbetuximab confirms the urgent therapeutic need and brings us one step closer to delivering on this commitment to patients, families and caregivers."

The BLA is based on results from the Phase 3 SPOTLIGHT and GLOW clinical trials. The SPOTLIGHT study evaluated zolbetuximab plus mFOLFOX6 (a combination regimen that includes oxaliplatin, leucovorin and fluorouracil) compared to placebo plus mFOLFOX6. The GLOW study evaluated zolbetuximab plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared to placebo plus CAPOX.

In both SPOTLIGHT and GLOW, approximately 38% of patients screened for the trials had tumors that were CLDN18.2-positive (≥75% of tumor cells with moderate-to-strong membranous CLDN18 staining intensity), as determined by a validated immunohistochemistry assay.3,4

Astellas has already reflected the impact from this acceptance in its financial forecast of the current fiscal year ending March 31, 2024.

About Locally Advanced Unresectable Metastatic Gastric and Gastroesophageal Junction Cancer
Gastric cancer, also commonly known as stomach cancer, is the fifth most commonly diagnosed cancer worldwide.5 In the U.S., it is estimated that 26,500 people will be diagnosed with gastric cancer and 11,130 will die from the disease in 2023.1 Signs and symptoms can include indigestion or heartburn, pain or discomfort in the abdomen, nausea and vomiting, diarrhea or constipation, bloating of the stomach after meals, loss of appetite, and sensation of food getting stuck in the throat while eating.2 Signs of more advanced gastric cancer can include unexplained weight loss, weakness and fatigue, and vomiting blood or having blood in the stool.6 Risk factors associated with gastric cancer can include older age, male gender, family history, H. pylori infection, smoking and gastroesophageal reflux disease (GERD).2,7 Because early-stage gastric cancer symptoms frequently overlap with more common stomach-related conditions, gastric cancer is often diagnosed in the advanced or metastatic stage, or once it has spread from the tumor’s origin to other body tissues or organs.2 The five-year relative survival rate for patients at the metastatic stage is 6.6%.1 Gastroesophageal junction (GEJ) adenocarcinoma is a cancer that starts at the area where the esophagus joins the stomach.8

About Zolbetuximab
Zolbetuximab is an investigational, first-in-class chimeric IgG1 monoclonal antibody (mAb) that targets and binds to Claudin 18.2 (CLDN18.2), a transmembrane protein. Zolbetuximab acts by binding to CLDN18.2 on the cancer cell surface of gastric epithelial cells. In pre-clinical studies, this binding interaction then induces cancer cell death by activating two distinct immune system pathways — antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).9 Zolbetuximab has not been approved by any regulatory bodies for the treatment of patients with gastric and GEJ cancers, and there is no guarantee the agent will receive regulatory approval or become commercially available for the uses being investigated.

INVESTIGATIONAL STUDIES

About SPOTLIGHT Phase 3 Clinical Trial
SPOTLIGHT is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab (IMAB362) plus mFOLFOX6 (a combination regimen that includes oxaliplatin, leucovorin and fluorouracil) compared to placebo plus mFOLFOX6 as a first-line treatment in patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2-positive. The study enrolled 565 patients at 215 study locations in the U.S., Canada, United Kingdom, Australia, Europe, South America and Asia. The primary endpoint is progression-free survival (PFS) in participants treated with the combination of zolbetuximab plus mFOLFOX6 compared to those treated with placebo plus mFOLFOX6. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), safety and tolerability and quality-of-life parameters.

Data from the SPOTLIGHT clinical trial were presented during the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal (GI) Cancers Symposium in an oral presentation on January 19 and were subsequently published in The Lancet on April 14.3

For more information, please visit clinicaltrials.gov under Identifier NCT03504397.

About GLOW Phase 3 Clinical Trial
GLOW is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab (IMAB362) plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared to placebo plus CAPOX as a first-line treatment in patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2-positive. The study enrolled 507 patients at 166 study locations in the U.S., Canada, United Kingdom, Europe, South America and Asia. The primary endpoint is PFS in participants treated with the combination of zolbetuximab plus CAPOX compared to those treated with placebo plus CAPOX. Secondary endpoints include OS, ORR, DOR, safety and tolerability and quality-of-life parameters.

Data from the GLOW study were initially presented at the March 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series with an updated oral presentation at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting on June 3.4

For more information, please visit clinicaltrials.gov under Identifier NCT03653507.

Investigational Pipeline in CLDN18.2
An expanded Phase 2 trial in metastatic pancreatic adenocarcinoma is in progress. The trial is a randomized, multi-center, open-label study, evaluating the safety and efficacy of investigational zolbetuximab in combination with gemcitabine plus nab-paclitaxel as a first-line treatment in patients with metastatic pancreatic adenocarcinoma with CLDN18.2-positive tumors (defined as ≥75% of tumor cells demonstrating moderate-to-strong membranous CLDN18 staining based on a validated immunohistochemistry assay). For more information, please visit clinicaltrials.gov under Identifier NCT03816163.

In addition to zolbetuximab, ASP2138 is under development in our Primary Focus Immuno-Oncology. ASP2138 is a bispecific monoclonal antibody that binds to CD3 and CLDN18.2, and it is currently in a Phase 1 trial for people with gastric, GEJ or pancreatic adenocarcinoma. The safety and efficacy of the agent under investigation have not been established for the uses being considered. For more information, please visit clinicaltrials.gov under Identifier NCT05365581.

There is no guarantee that the agent will receive regulatory approval and become commercially available for the uses being investigated.