1stOncology™: Cancer Intelligence Service – Page 753 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Poseida Therapeutics, Inc. Announces Agreement to be Acquired by Roche Holdings, Inc.

On November 26, 2024 Poseida Therapeutics, Inc. (Nasdaq: PSTX) ("Poseida"), a clinical-stage allogeneic cell therapy and genetic medicines company advancing differentiated non-viral treatments for patients with cancer, autoimmune and rare diseases, reported that it has entered into a merger agreement to be acquired by Roche Holdings, Inc. ("Roche") at a price of $9.00 per share in cash at closing, plus a non-tradeable CVR to receive certain contingent payments of up to an aggregate of $4.00 per share in cash upon achievement of specific milestones (Press release, Poseida Therapeutics, NOV 26, 2024, View Source [SID1234648626]). This corresponds to a total equity value of approximately $1.5 billion on a fully diluted basis. The merger agreement has been unanimously approved by Poseida’s Board of Directors, and Poseida’s Board of Directors unanimously recommends that Poseida stockholders tender their shares in the tender offer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

The proposed acquisition will establish a new core capability for Roche in allogeneic cell therapy, with lead opportunities focused on CAR-T programs covered by the existing strategic collaboration between Poseida and Roche in hematologic malignancies. It will include CAR-T programs for solid tumors and autoimmune diseases, along with Poseida’s genetic engineering platform and related preclinical medicines.

Poseida has pioneered a proprietary technology platform that includes a full set of non-viral capabilities to design, develop and manufacture allogeneic, T stem cell memory cells (TSCM)-rich CAR-T therapies. TSCM cells are considered ideal for CAR-T therapy because they are long-lived, multi-potent and self-replicating, with the potential for an improved safety and efficacy profile. This may offer benefits compared to other approaches, which either use a different cell type or drive T cell differentiation (and therefore less stemness) as part of the process to manufacture the CAR-T cells.

"Poseida has demonstrated the unique ability of its proprietary non-viral technology platform to create allogeneic, TSCM-rich CAR-T therapies with the potential to improve clinical outcomes and expand access to this important class of medicines. Most recently, this was highlighted by the compelling interim clinical data for P-BCMA-ALLO1 in patients with multiple myeloma," said Kristin Yarema, Ph.D., President and Chief Executive Officer of Poseida Therapeutics. "We have worked closely with Roche through our collaboration focused on hematologic malignancies, and we are excited to join Roche to work as colleagues together across our pipeline and future programs. Roche’s global capabilities in late-stage development and commercialization will enable patients worldwide to benefit from the transformative potential of allo CAR-T."

Poseida and its employees will join the Roche Group as part of Roche’s Pharmaceuticals Division.

Transaction Terms

Under terms of the merger agreement, Roche will commence a tender offer to acquire all of Poseida’s outstanding shares for a price of $9.00 per share in cash at closing, plus a non-tradeable CVR to receive up to an aggregate of $4.00 per share in cash, payable upon achievement of specified milestones.

The closing of the transaction is subject to customary closing conditions, including the tender of shares representing at least a majority of Poseida’s outstanding shares (other than shares held by Poseida, Roche or any of their respective subsidiaries, and any dissenting shares), the completion of regulatory review and other customary closing conditions. Upon the successful completion of the tender offer, Roche will acquire all remaining Poseida shares that are not tendered into the tender offer through a second-step merger at the same price of $9.00 per share in cash at closing, plus a non-tradeable CVR to receive up to an aggregate of $4.00 per share in cash, payable upon achievement of specified milestones.

The closing of the transaction is currently expected to take place in the first quarter of 2025.

Advisors
Centerview Partners LLC is serving as exclusive financial advisor to Poseida and Cooley LLP is serving as legal counsel. Citi is acting as financial advisor to Roche and Sidley Austin LLP is acting as legal counsel to Roche.

Roche reports update on Phase III SKYSCRAPER-01 study results

On November 26, 2024 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported an update on the phase III SKYSCRAPER-01 study, evaluating tiragolumab combined with Tecentriq (atezolizumab) compared to Tecentriq alone for patients with PD-L1-high, locally advanced or metastatic non-small cell lung cancer (NSCLC) (Press release, Hoffmann-La Roche, NOV 26, 2024, View Source [SID1234648622]).

SKYSCRAPER-01 is a global phase III, randomised, double-blind study evaluating tiragolumab plus Tecentriq compared to Tecentriq alone in 534 patients with PD-L1-high previously untreated, locally advanced unresectable or metastatic NSCLC. Patients were randomised 1:1 to receive either tiragolumab plus Tecentriq or placebo plus Tecentriq, until disease progression, loss of clinical benefit, or unacceptable toxicity. The study did not reach the primary endpoint of overall survival at the final analysis. The overall safety profile observed remained consistent with longer follow-up, and no new safety signals were identified. The detailed data will be presented at a medical meeting in 2025.

Roche continuously reviews its study programmes to determine if any adjustments are necessary for the purposes of ongoing research. Roche will apply the same principles to this programme, with additional data from phase III studies across different settings or tumour types anticipated next year.

About tiragolumab
Tiragolumab is an investigational immune checkpoint inhibitor with an intact Fc region. Tiragolumab selectively binds to TIGIT, a novel inhibitory immune checkpoint which suppresses the immune response to cancer.

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to bind to PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells.

Shorla Oncology Announces FDA Approval of IMKELDI (imatinib) Oral Solution, an Oral Liquid for the Treatment of Certain Forms of Leukemia and Other Cancers

On November 25, 2024 Shorla Oncology (‘Shorla’), a U.S.-Ireland specialty pharmaceutical company, reported that the FDA has approved IMKELDI (imatinib) oral solution, the first oral liquid form of imatinib to treat certain forms of leukemia and other cancers (Press release, Shorla Oncology, NOV 25, 2024, View Source [SID1234648642]).

"We are thrilled to offer an oral solution option for patients with leukemia and other cancers, a meaningful advancement for thousands in need," said Sharon Cunningham, chief executive officer of Shorla. "Oral solutions may ensure more precise and consistent dosing, offering a convenient alternative to compounding for patients who have difficulty swallowing or require dosing tailored to body surface area."

Leveraging Shorla’s novel technology, IMKELDI is an advanced liquid formulation of imatinib designed to provide dosing accuracy. IMKELDI can help slow or prevent the growth of specific cancers, including chronic myeloid leukemia (CML) and acute lymphoblastic leukemia, myelodysplastic syndrome /myeloproliferative disease (MDS/MPD), and gastrointestinal tumors (GIST).

In 2024, an estimated 9,280 people will be diagnosed with CML1, over 10,000 with MDS/MPD2, and up to 6,000 with GIST3 in the U.S. Despite the proven clinical benefits of imatinib, patient adherence can be an issue,4,5 underscoring a critical unmet need for a more accessible, patient-friendly oral solution delivery system.

"This milestone marks our fourth FDA approval as we advance our mission to make existing oncology treatments better through formulation re-innovation," said Orlaith Ryan, chief technical officer and co-founder of Shorla. "Our team is dedicated to creating more patient-friendly options that address real needs in those suffering from cancer."

Rayna Herman, chief commercial officer of Shorla added, "At Shorla, every innovation is driven by our commitment to put patients first. IMKELDI is another step forward as we continue to expand our growing portfolio with products that prioritize accessibility and affordability."

1. Key Statistics for Chronic Myeloid Leukemia. American Cancer Society. Updated January 17, 2024. Accessed November 7, 2024. View Source
2. Key Statistics for Myelodysplastic Syndromes. American Cancer Society. Updated January 22, 2018. Accessed November 7, 2024. View Source
3. Key Statistics for Gastrointestinal Stromal Tumors American Cancer Society. Updated January 26, 2021. Accessed November 7, 2024. View Source
4. Yanamandra U, Malhotra P, Sahu KK, et al. Variation in Adherence Measures to Imatinib Therapy. J Glob Oncol. 2018;4:1-10. doi:10.1200/JGO.2016.007906
5. Al-Barrak J, Cheung WY. Adherence to imatinib therapy in gastrointestinal stromal tumors and chronic myeloid leukemia. Support Care Cancer. 2013;21(8):2351-2357. doi:10.1007/s00520-013-1831-6

About IMKELDI

IMKELDI is an oral solution of imatinib mesylate, a tyrosine kinase inhibitor, approved by the U.S. Food and Drug Administration for use in certain forms of leukemia (such as acute lymphoblastic leukemia and chronic myeloid leukemia) and other cancers in adults and pediatric patients as young as one year old. Featuring a convenient, palatable strawberry flavor and a stable formulation that does not require refrigeration, IMKELDI offers a patient-friendly, precise treatment option designed to improve adherence and accessibility.

D3 Bio’s D3S-001 Demonstrates Significantly Improved Covalent Potency in Depleting Cellular Active KRAS in Pre-Clinical and Clinical Studies in KRAS G12C-Mediated Cancers

On November 25, 2024 D3 Bio, a global clinical stage biotechnology company focusing on discovery, development, and registration of innovative cancer drugs, reported that its lead compound, a next-generation KRAS G12C inhibitor, D3S-001, demonstrated rapid target engagement, overcame the limiting factors of nucleotide cycling and RTK activation, and showed robust preclinical and clinical activities in KRAS G12C-mediated cancers, in a study published in Cancer Discovery (Press release, D3 Bio, NOV 25, 2024, View Source [SID1234648641]).

In a paper titled, "A KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities", researchers from D3 Bio and its collaborators demonstrated that D3S-001 performed significantly better than other KRAS G12C inhibitors in multiple pre-clinical and clinical studies designed to profile the class of KRAS G12C small molecule inhibitors. Specifically, D3S-001 demonstrated substantially improved covalent potency and better and faster target engagement (TE) kinetics, compared to the approved drugs (sotorasib and adagrasib) in the class. This suggests that D3S-001 has the potential to "lock" KRAS G12C in its inactive (GDP-bound) state more efficiently, possibly resulting in cellular active KRAS depletion in clinically relevant doses. In addition, D3S-001’s high potency and rapid kinetics allow it to block the GDP-to-GTP transition even in the presence of growth factors. In contrast, first-generation G12C inhibitors are less effective in these conditions, which may contribute to their limited clinical efficacy.

In cell line and patient-derived tumor xenograft models across multiple cancer types, D3S-001 demonstrated significantly more robust anti-tumor responses than the other KRAS G12C inhibitors in the study. Importantly, these include a delay in disease progression in tumors that were resistant to an FDA-approved KRAS G12C inhibitor. D3S-001 also exhibited brain penetration properties, resulting in durable intracranial tumor regression in mouse models with brain metastases.

Citing the ongoing D3S-001 Phase 1/2 trial in KRAS G12C-mediated solid tumors, the study noted that durable RECIST responses were observed across all dose cohorts, as well as systemic and intracranial anti-tumor activity in two highlighted patients with non-small cell lung cancer (NSCLC) enrolled in the first dose cohort of this trial.

The researchers conclude that D3S-001 is a next-generation GDP-bound KRAS G12C inhibitor with robust antitumor preclinical activity and promising durable responses in the ongoing clinical trial, which could overcome the limitations of the first-generation drugs.

Separately, in an oral presentation at the ESMO (Free ESMO Whitepaper) Congress 2024, dose-escalation data from the D3S-001 Phase 1 clinical trial in 42 patients of locally advanced or metastatic KRAS G12C-mutated cancers with prior systemic treatments was presented. The presenter and trial investigator, Byoung Chul Cho, MD, PhD, Professor in the Division of Medical Oncology at Yonsei Cancer Center, Yonsei University College of Medicine and Chief of Lung Cancer Center at Yonsei Cancer Center, Yonsei University College of Medicine, highlighted that D3S-001 functionally abolishes the KRAS G12C transition from GDP-bound (inactive) state to the GTP-bound (active) state, depleting cellular active KRAS, even in the presence of growth factor stimulation. Results from the Phase 1a dose-escalation study (42 patients in total) showed favorable tolerability across different dose levels, with no maximum-tolerated dose reached. In addition, D3S-001 demonstrated consistent and promising efficacy in the G12C-inhibitor naïve population, with a confirmed overall response rate (ORR) of 73.5% across tumor types. Researchers also observed brain tumor shrinkage in patients with brain metastases and a rapid, sustained reduction of mutant allele frequency (MAF), which measures mutated genes, in circulating tumor cell DNA (ctDNA) as early as Day 8 post-treatment. Expansion study cohorts are ongoing and focus on monotherapy and combination therapy regimens in non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC).

"While promising, the first generation of KRAS G12C inhibitor class has exhibited limited durability in the clinic, which could be addressed by a more efficient mode of action," said Dr. Cho. "This paper, demonstrating that D3S-001 has a more robust covalent potency and rapid target engagement kinetics, unaffected by RTK activation, unveils a novel mode of action that correlates with pre-clinical anti-tumor activity and promising Phase 1 clinical results. Furthermore, the study shows, for the first time, that GDP-bound KRAS G12C inhibitors can deplete cellular-active KRAS as efficiently the GTP-bound inhibitor class, suggesting that D3S-001 could address the issues that have challenged this class of drugs."

"Believing that a next-generation KRAS-G12C inhibitor with significantly improved target inhibition efficiency could become the backbone of a new standard of care for cancers carrying KRAS G12C mutations and provide profound clinical advantages, we selected D3S-001 for its superior covalent potency and differentiated target engagement kinetics," said George Chen, MD, Founder, Chairman and CEO, D3 Bio. "This study validates our strategy of discovering a next-generation and differentiated G12C inhibitor with rapid target engagement to deliver more efficacious clinical activity. At the ESMO (Free ESMO Whitepaper) 2024 Congress, we presented Phase 1 data from 42 patients, showing a consistent and clinically meaningful response across all cancer types. We are excited with the progress of D3S-001, a potential best-in-class compound, and expect to report topline Phase 2 data in 2025."

About D3S-001

D3S-001 is a next-generation KRAS G12C inhibitor designed to enhance KRAS G12C target engagement. In preclinical investigations, D3S-001 has demonstrated high covalent potency, the ability to rapidly and completely engage the KRAS G12C target at clinically relevant doses and CNS penetration properties. D3S-001 is currently in a Phase 2 global clinical trial in patients with advanced solid tumors harboring a KRAS G12C mutation, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and other tumor types. For detailed information about D3S-001, please refer to the highlighted Research Article published at the 2024 September issue of Cancer Discovery, titled "D3S-001, A KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities" (Cancer Discovery 1 September 2024; 14 (9): 1675–1698. View Source). D3S-001 has received US FDA Orphan Drug Designation (ODD) for the treatment of pancreatic cancer and Fast Track Designation (FTD) for the treatment of late-line non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).

For more on the D3S-001 clinical trial, please go to: View Source;rank=1

Janux Therapeutics to Host Virtual Event Discussing Updated Clinical Data in Phase 1a Dose Escalation for JANX007 in mCRPC and Doses Selected for Phase 1b Expansion Studies

On November 25, 2024 Janux Therapeutics, Inc. (Nasdaq: JANX) (Janux), a clinical-stage biopharmaceutical company developing a broad pipeline of novel immunotherapies by applying its proprietary technology to its Tumor Activated T Cell Engager (TRACTr) and Tumor Activated Immunomodulator (TRACIr) platforms, reported it will host a virtual event on Monday, December 2, 2024, at 4:30 PM ET (Press release, Janux Therapeutics, NOV 25, 2024, View Source [SID1234648640]).

David Campbell, Ph.D., President & Chief Executive Officer, will provide an update on JANX007 Phase 1a dose escalation data and doses selected for Phase 1b expansion studies in adult subjects with metastatic castration-resistant prostate cancer (mCRPC).

A live question and answer session will follow the formal presentation. To register for the event, please click here.

Participant Dial-In Details:
USA & Canada – (800) 715-9871
International – 1 (646) 307-1963
Conference ID: 2229349

Janux’s TRACTr and TRACIr Pipeline

Janux’s first clinical candidate, JANX007, is a TRACTr that targets PSMA and is being investigated in a Phase 1 clinical trial in adult subjects with metastatic castration-resistant prostate cancer (mCRPC). Janux’s second clinical candidate, JANX008, is a TRACTr that targets EGFR and is being studied in a Phase 1 clinical trial for the treatment of multiple solid cancers including colorectal carcinoma, squamous cell carcinoma of the head and neck, non-small cell lung cancer, renal cell carcinoma, small cell lung cancer, pancreatic ductal adenocarcinoma and triple-negative breast cancer. We are also generating a number of additional TRACTr and TRACIr programs for potential future development, some of which are at development candidate stage or later. We are currently assessing priorities in our preclinical pipeline.