On December 4, 2023 Exelixis, Inc. (Nasdaq: EXEL) and Arcus Biosciences (NYSE: RCUS) reported that the companies have entered into a clinical trial collaboration for STELLAR-009, a phase 1b/2 trial evaluating zanzalintinib, Exelixis’ next-generation tyrosine kinase inhibitor (TKI), in combination with AB521, an inhibitor of the transcription factor HIF-2⍺, in patients with advanced solid tumors, including clear cell renal cell carcinoma (ccRCC) (Press release, Exelixis, DEC 4, 2023, View Source [SID1234638124]). Exelixis is sponsoring STELLAR-009, and Arcus is co-funding the study and providing AB521 for use in the trial. Patient enrollment for STELLAR-009 is expected to begin before the end of 2023.

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"We are excited to learn more about the potential effects of zanzalintinib plus Arcus’ HIF-2⍺ inhibitor, as these two molecules approach the inhibition of cancer cell proliferation and tumor angiogenesis from differing angles, and combination therapy may provide better outcomes than either therapy alone," said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. "We have a long-established commitment to advancing treatment options in kidney cancer, and we are eager to maximize the potential of zanzalintinib through this collaboration with Arcus and look forward to advancing the combination in the clinic."

"We are excited to partner with Exelixis on the STELLAR-009 study to determine the best-in-class potential of AB521 in combination with zanzalintinib and look forward to generating a robust set of data to move this combination into full development," said Dimitry S.A. Nuyten, M.D., Ph.D., Chief Medical Officer of Arcus Biosciences. "The STELLAR-009 study is an important step in the development of AB521 and enables a cost-effective path to evaluating our HIF-2⍺ inhibitor with a next-generation TKI."

The dose-finding stage of this open-label study will determine a recommended dose for zanzalintinib in combination with AB521 in patients with advanced solid tumors and in patients with advanced ccRCC. Expansion cohorts will further evaluate the tolerability and activity of this combination in ccRCC as well as investigate the contribution of components, supported by activity data generated from monotherapy studies in ccRCC patients, to support full development.

More information about this trial will be available soon on ClinicalTrials.gov.

About Zanzalintinib
Zanzalintinib is a next-generation oral TKI that inhibits the activity of receptor tyrosine kinases implicated in cancer growth and spread, including VEGF receptors, MET, AXL and MER. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis and resistance to multiple therapies, including immune checkpoint inhibitors (ICIs). With zanzalintinib, Exelixis sought to build upon its extensive experience with the target profile of cabozantinib, the company’s flagship medicine, while improving key characteristics, including pharmacokinetic half-life. Zanzalintinib is currently being developed for the treatment of advanced solid tumors, including genitourinary, colorectal and head and neck cancers.

About AB521
AB521 is a small molecule inhibitor of HIF-2⍺, a transcription factor involved in oxygen sensing in multiple organs as well as in tumors. Clear cell RCC is almost universally associated with HIF-2⍺ dysregulation as a result of genetic abnormalities in the VHL pathway. This creates a situation of pseudohypoxia and the abnormal increase in HIF-2⍺-mediated expression of a wide array of proteins involved in cancer cell proliferation and survival, treatment resistance and angiogenesis. Arcus is currently evaluating AB521 in ARC-20, a phase 1/1b study in cancer patients. Enrollment for the dose-expansion stage in ccRCC patients is complete for the target dose of 100 mg, and efficacy data from this stage are expected in 2024. In the dose-escalation stage up to 100 mg, as of December 1, 2023, pharmacokinetic and pharmacodynamic data were consistent with the data generated in healthy volunteers, and no dose-limiting toxicities were observed. AB521 has the potential to achieve substantially greater HIF-2⍺ inhibition than the approved dose of the marketed competitor.

About RCC
Kidney cancer is among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 An estimated 81,800 Americans will be diagnosed with kidney cancer in 2023.1 Clear cell RCC is the most common type of kidney cancer in adults.2 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 15%.3 In 2022, approximately 32,200 patients with advanced kidney cancer required systemic therapy in the U.S., with over 20,000 patients receiving first-line treatment.

On December 4, 2023 Eli Lilly and Company (NYSE: LLY) reported the extension of the expiration of the tender offer to acquire all of the issued and outstanding shares ("Shares") of common stock of POINT Biopharma Global Inc. (NASDAQ: PNT), for a purchase price of $12.50 per share in cash, without interest and less any applicable tax withholding (Press release, Eli Lilly, DEC 4, 2023, View Source [SID1234638123]).

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The tender offer, which was previously scheduled to expire at 5:00 p.m., Eastern time, on Dec. 1, 2023, has been extended until 5:00 p.m., Eastern time, on Dec. 15, 2023, unless the tender offer is further extended or earlier terminated, in order for the parties to satisfy the minimum tender condition. All regulatory approvals necessary for the consummation of the transaction have been obtained.

Computershare Trust Company, N.A., the depositary and paying agent for the tender offer, has advised Lilly that, as of 5:00 p.m., Eastern time, on Dec. 1, 2023, approximately 26,374,912 Shares have been validly tendered and not properly withdrawn in the tender offer, representing approximately 24.75% of the issued and outstanding Shares, as of such date and time. Holders that have previously tendered their Shares do not need to re-tender their Shares or take any other action in response to the extension of the tender offer. Questions or requests for assistance may be directed to Georgeson LLC, the information agent for the tender offer, by calling toll free 1-800-932-9864 or via email to [email protected].

On December 4, 2023 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported an update on its immuno-oncology pipeline of CRISPR/Cas9 gene-edited allogeneic chimeric antigen receptor (CAR) T cell product candidates (Press release, CRISPR Therapeutics, DEC 4, 2023, View Source [SID1234638122]).

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The Company’s first-generation allogeneic CAR T candidates, CTX110 and CTX130, provided important proof of concept that allogeneic CAR T cells can produce durable remissions following a standard lymphodepletion regimen. Preliminary data from ongoing clinical trials of its next-generation candidates, CTX112 targeting CD19 and CTX131 targeting CD70, suggest that these candidates may improve upon that clinical profile. Emerging pharmacology data, including pharmacokinetics, indicate that the novel potency gene edits in CTX112 and CTX131 lead to significantly higher CAR T cell expansion and functional persistence in patients compared to the first-generation candidates. In addition, the next-generation candidates exhibit increased manufacturing robustness, with a higher and more consistent number of CAR T cells produced per batch. Based on these considerations, the Company is focusing on the development of CTX112 and CTX131 and will be transitioning patients treated with CTX110 and CTX130 to long-term follow-up where applicable.

"Our next-generation allogeneic CAR T candidates reflect our mission of innovating continuously to bring potentially transformative medicines to patients as quickly as possible," said Samarth Kulkarni, Ph.D., Chief Executive Officer and Chairman of the Board of CRISPR Therapeutics. "We are excited about our next-generation CAR T platform, and focusing our efforts on these candidates will allow us to advance these potentially best-in-class CAR T therapies more efficiently and rapidly."

"We are very encouraged by the progress and early clinical data from our next-generation candidates. While we saw benefits from consolidation dosing with CTX110, we believe CTX112 could result in even better outcomes for patients," said PK Morrow, M.D., Chief Medical Officer of CRISPR Therapeutics. "We thank the patients, families, and investigators who have participated in our clinical trials of CTX110 and CTX130 and look forward to applying learnings from these programs to expedite the development of CTX112 and CTX131."

In December 2022, the Company presented data from Part A of the Phase 1/2 clinical trial of CTX110 that showed the potential for CTX110 to produce durable complete remissions in heavily pre-treated patients following a standard lymphodepletion regimen. In new data updated today, Part B of the trial demonstrated an increased 6-month complete response (CR) rate following the inclusion of consolidation dosing, as shown in the table below. The safety profile of CTX110 in Part B remained consistent with the positively differentiated safety profile observed in Part A.

Part A
Single dose with optional
re-dosing at ≥DL3 (N=27) Part B
Consolidation dosing at
DL4 (N=31)
ORR 67% 65%
CR rate 41% 39%
6-month CR rate 19% 23%

CTX112 and CTX131 have the potential to improve upon the efficacy observed with CTX110 and CTX130. These next-generation candidates each incorporate two novel gene edits—knock-out of Regnase-1 and transforming growth factor-beta receptor type 2 (TGFBR2)—that have the potential to enhance CAR T potency and reduce CAR T exhaustion. Editing Regnase-1 removes an intrinsic "brake" on T cell function while editing TGFBR2 removes a key extrinsic "brake" on T cell anti-tumor activity. CRISPR Therapeutics identified this combination of edits through systematic screening of dozens of new and previously described genes. In preclinical studies, these edits synergistically improved potency approximately 10-fold compared to the first-generation candidates. Clinical trials are ongoing for CTX112 in B-cell malignancies and for CTX131 in solid tumors. The Company is producing CTX112 and CTX131 for clinical trials at its internal GMP manufacturing facility.

Furthermore, CRISPR Therapeutics announced plans to initiate new clinical trials of CTX112 and CTX131 in additional indications. The Company plans to expand the evaluation of CTX112 beyond oncology into autoimmune diseases. Early clinical studies have shown that CD19-directed autologous CAR T therapy can produce long-lasting remissions in multiple autoimmune indications. CTX112 has the potential to provide similar results with several advantages, including greater scalability, lower cost of goods, and no patient apheresis. The Company plans to initiate a clinical trial in systemic lupus erythematosus (SLE) in the first half of 2024, with the potential to expand into additional autoimmune indications in the future.

About CD19 Candidates
CTX110 is a wholly-owned, healthy donor-derived gene-edited allogeneic CAR T investigational therapy targeting cluster of differentiation 19, or CD19, and CTX112 is a next-generation, wholly-owned, allogeneic CAR T product candidate targeting CD19, which incorporates additional edits designed to enhance CAR T potency and reduce CAR T exhaustion. CTX112 is being investigated in an ongoing clinical trial designed to assess safety and efficacy of the product candidate in adult patients with relapsed or refractory CD19-positive B-cell malignancies who have received at least two prior lines of therapy.

About CD70 Candidates
CTX130 is a wholly-owned, healthy donor-derived gene-edited allogeneic CAR T investigational therapy targeting cluster of differentiation 70, or CD70, an antigen expressed on various solid tumors and hematologic malignancies, and CTX131 is a next-generation, wholly-owned, allogeneic CAR T product candidate targeting CD70, which incorporates additional edits designed to enhance CAR T potency and reduce CAR T exhaustion. CTX131 is being investigated in a clinical trial designed to assess the safety and efficacy of the product candidate in adult patients with relapsed or refractory solid tumors.

On December 4, 2023 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported the details of its investor webcast being held Monday, December 11, 2023 at 8:00 a.m. ET (5:00 a.m. PT) (Press release, Cogent Biosciences, DEC 4, 2023, View Source [SID1234638121]). The SUMMIT data are being presented in an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on December 9, 2023 at 1:30 p.m. ET (10:30 a.m. PT), and the APEX data are being presented in a poster session on December 11, 2023.

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The webcast event will be led by Andrew Robbins, Cogent’s President and Chief Executive Officer and will include a SUMMIT data presentation by PD Dr. Frank Siebenhaar, M.D., Head University Outpatient Clinic, Institute of Allergology, Charité – Universitätsmedizin Berlin and an APEX data presentation by Pankit Vachhani, M.D., assistant professor in the University of Alabama at Birmingham Department of Medicine, Division of Hematology and Oncology.

The live webcast can be accessed on the Investors and Media page of Cogent’s website at investors.cogentbio.com/events. A replay of the webcast will be available approximately two hours after the completion of the event and will be archived for up to 30 days.

On December 4, 2023Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CANF), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address oncological and inflammatory diseases, reported that it completed the design of a Phase IIa study protocol for the treatment of patients with pancreatic cancer and plans to submit the protocol shortly to ethical committees for approval (Press release, Can-Fite BioPharma, DEC 4, 2023, View Source [SID1234638119]).

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Can-Fite completed the protocol design of the CF102-222PC clinical study entitled: "A Phase II Open-Label Study of the Safety and Activity of Namodenoson in the Treatment of Advanced Pancreatic Adenocarcinoma".

This is a multicenter open-label trial in patients with advanced pancreatic adenocarcinoma whose disease has progressed on at least 1st-line therapy or who refuse standard treatment. The trial will evaluate the safety, clinical activity, and pharmacokinetics (PK) of Namodenoson in this population. All patients will receive oral Namodenoson 25 mg administered twice daily for consecutive 28-day cycles. Patients will be evaluated regularly for safety. Approximately 20 evaluable patients will be enrolled. The primary objective of this trial is to characterize the safety profile of Namodenoson and the secondary objective is to evaluate the clinical activity as determined by the Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), Progression-Free Survival (PFS), Disease Control Rate (DCR), Duration of Response (DoR), and Overall Survival (OS).

The study will be conducted by Dr. Salomon Stemmer, a leading key opinion leader, at the Institute of Oncology, Rabin Medical Center, Israel.

"This Phase IIa study is designed as an open-label one, enabling us to assess the safety and potential efficacy of Namodenoson in pancreatic cancer patients whose disease has progressed despite first-line treatment. Our positive Namodenoson data in pancreatic carcinoma experimental models together with the positive data in the Phase II advanced liver cancer study, with a patient showing overall survival of 7 years, encouraged us to initiate the current Phase IIa study," stated Can-Fite’s Medical Director Dr. Michael Silverman.

Namodenoson recently received peer-reviewed recognition for its efficacy findings in pancreatic cancer including from the American Association of Cancer Research (AACR) (Free AACR Whitepaper) which accepted Can-Fite’s study titled "Namodenoson Inhibits the Growth of Pancreatic Carcinoma via De-regulation of the Wnt/β-catenin Signaling Pathway" for a poster presentation at the AACR (Free AACR Whitepaper) Special Conference on Pancreatic Cancer, and from Biomolecules, a scientific journal focused on the function and mechanism of bioactive molecules, which published an article titled "Namodenoson Inhibits the Growth of Pancreatic Carcinoma via Deregulation of the Wnt/β-catenin, NF-κB, and RAS Signaling Pathways".

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson was evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.