On December 26, 2023 AstraZeneca reported that it has entered into a definitive agreement to acquire Gracell Biotechnologies Inc. (Gracell, NASDAQ: GRCL), a global clinical-stage biopharmaceutical company developing innovative cell therapies for the treatment of cancer and autoimmune diseases, furthering the AstraZeneca cell therapy ambition.

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The proposed acquisition will enrich AstraZeneca’s growing pipeline of cell therapies with GC012F, a novel, clinical-stage FasTCAR-enabled BCMA and CD19 dual-targeting autologous chimeric antigen receptor T-cell (CAR-T) therapy, a potential new treatment for multiple myeloma, as well as other haematologic malignancies and autoimmune diseases including systemic lupus erythematosus (SLE).

Autologous CAR-T is a type of cell therapy created by reprogramming a patient’s immune T cells to target disease-causing cells, and the manufacturing process for this type of treatment is complex and time-consuming. The Gracell FasTCAR platform significantly shortens manufacturing time, enhances T cell fitness, and will potentially improve the effectiveness of autologous CAR-T treatment in patients. Future applications of this technology may also include rare diseases.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "The proposed acquisition of Gracell will complement AstraZeneca’s existing capabilities and previous investments in cell therapy, where we have established our presence in CAR-T and T-cell receptor therapies (TCR-Ts) in solid tumours. GC012F will accelerate our cell therapy strategy in haematology, with the opportunity to bring a potential best-in-class treatment to patients living with blood cancers using a differentiated manufacturing process, as well as exploring the potential for cell therapy to reset the immune response in autoimmune diseases."

Dr. William Cao, founder, Chairman and CEO, Gracell, said: "We look forward to working with AstraZeneca to accelerate our shared goal of bringing transformative cell therapies to more patients living with debilitating diseases. By combining our expertise and resources, we can unlock new ways to harness the Gracell FasTCAR manufacturing platform, which we believe has the potential to optimise the therapeutic profile of engineered T cells, to pioneer the next generation of autologous cell therapies."

Gracell will operate as a wholly owned subsidiary of AstraZeneca, with operations in China and the US.

Financial considerations

Under the terms of the definitive agreement, AstraZeneca will acquire all of Gracell’s fully diluted share capital (including shares represented by ADSs) through a merger for a price of $2.00 per ordinary share in cash at closing (equivalent to $10.00 per ADS of Gracell) plus a non-tradable contingent value right of $0.30 per ordinary share (equivalent to $1.50 per ADS of Gracell) in cash payable upon achievement of a specified regulatory milestone.

The upfront cash portion of the consideration represents a transaction value of approximately $1.0bn, a 62% premium to Gracell’s closing market price on 22nd December 2023 and a 154% premium to the 60-day volume-weighted average price (VWAP) of $3.94 before this announcement. Combined, the upfront and potential contingent value payments represent, if achieved, a transaction value of approximately $1.2bn, an 86% premium to Gracell’s closing market price on 22nd December 2023 and a 192% premium to the 60-day VWAP. As part of the transaction, AstraZeneca will acquire the cash, cash equivalents and short-term investments on Gracell’s balance sheet, which totalled $234.1m as of 30th September 2023.

The transaction is expected to close in the first quarter of 2024, subject to customary closing conditions, including regulatory clearances, and Gracell shareholder approval. The transaction does not impact AstraZeneca’s financial guidance for 2023.

Notes

About GC012F

GC012F is Gracell’s FasTCAR-enabled BCMA/CD19 dual-targeting autologous CAR-T cell therapy, which aims to transform cancer and autoimmune disease treatment by seeking to drive deep and durable responses with an improved safety profile. GC012F is currently being evaluated in clinical studies in multiple haematologic malignancies and autoimmune diseases. Gracell has initiated a Phase Ib/II trial evaluating GC012F for the treatment of relapsed or refractory multiple myeloma in the US.

On December 26, 2023 Amgen (NASDAQ:AMGN) reported that the U.S. Food and Drug Administration (FDA) has completed its review of the company’s supplemental New Drug Application seeking full approval of LUMAKRAS (sotorasib) (Press release, Amgen, DEC 26, 2023, View Source [SID1234638791]). This review, which resulted in a Complete Response Letter, was based on the CodeBreaK 200 trial results for the treatment of adults with previously treated locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC). The FDA also issued a new postmarketing requirement (PMR) for an additional confirmatory study to support full approval that will be completed no later than February 2028.

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In addition, the FDA concluded that the dose comparison PMR issued at the time of LUMAKRAS accelerated approval, to compare the safety and efficacy of LUMAKRAS 960 mg daily dose versus a lower daily dose, has been fulfilled. The company said LUMAKRAS at 960 mg once-daily will remain the dose for patients with KRAS G12C-mutated NSCLC under accelerated approval.

In May 2021, LUMAKRAS was the first KRASG12C inhibitor to receive regulatory approval in the U.S., under accelerated approval. To date, over 15,000 patients worldwide have received LUMAKRAS/LUMYKRAS through the clinical development program, early access and commercial use.

About Advanced Non-Small Cell Lung Cancer and the KRAS G12C Mutation
Lung cancer is the leading cause of cancer-related deaths worldwide, and it accounts for more deaths worldwide than colon cancer, breast cancer and prostate cancer combined.1

KRAS G12C is the most common KRAS mutation in NSCLC.2 About 13% of patients with non-squamous NSCLC harbor the KRAS G12C mutation.3 Unmet medical need remains high and treatment options are limited for NSCLC patients with the KRAS G12C mutation whose first-line treatment has failed to work or has stopped working.

LUMAKRAS (sotorasib) U.S. Indication
LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

LUMAKRAS (sotorasib) Important U.S. Safety Information

Hepatotoxicity

LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
Monitor liver function tests (ALT, AST and total bilirubin) prior to the start of LUMAKRAS every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations.
Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.
Interstitial Lung Disease (ILD)/Pneumonitis

LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100, ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients.
Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified.
Most Common Adverse Reactions

The most common adverse reactions occurring in ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough.
Drug Interactions

Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products.
Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS.
If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid.

Please see LUMAKRAS full Prescribing Information.

On December 25, 2023 Suzhou Ribo Life Science Co. Ltd. ("Ribo"), an innovative clinical stage R&D company devoted to the development of nucleic acid drugs and related products based on the RNA interference (RNAi) technology, reported a landmark licensing agreement with Qilu Pharmaceutical Co., Ltd. ("Qilu") (Press release, Suzhou Ribo Life Science, DEC 25, 2023, View Source [SID1234638827]). The partnership grants Qilu the rights to develop, manufacture, and commercialize RBD7022, an oligonucleotide therapeutic targeting PCSK9, within the Greater China region, encompassing Mainland China, Hong Kong, and Macau.

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RBD7022 is a GalNAc-conjugated siRNA (small interfering RNA) drug developed leveraging Ribo’s proprietary RIBO-GalSTARTM platform. RBD7022 inhibits PCSK9 protein expression to reduce levels of LDL-C (low-density lipoprotein cholesterol) by preventing the lysosomal degradation of LDL receptors (LDL-R). RBD7022 is intended for treating familial hypercholesterolemia as well as atherosclerotic cardiovascular disease patients inadequately controlled by statin therapy and is currently under Phase I clinical trial. RBD7022 has demonstrated significant safety, tolerability, and lipid-lowering efficacy that could allow for extended dosing intervals spanning several months, thereby greatly improves patients’ compliance.

Dr. Weikang Tao, Vice President of Qilu and President of the Global Innovative R&D System, remarked: " Qilu is enthusiastically building a leading pipeline of innovative drugs, continually powering forward in therapeutic areas including cardio vasculature to meet unfulfilled clinical needs and enhance our product offerings in various domains. Ribo stands as a leader in development of oligonucleotide therapeutics in China. Collaborating with Ribo, leveraging the innovation to benefit our broad patient across China, is extremely gratifying. We are eager to combine strengths with Ribo in the field of oligonucleotides and expedite the market introduction of this promising new drug to capitalize on the opportunity in the Chinese market and realize our shared vision for a win-win cooperation."

Dr. Zicai Liang, Founder and CEO of Ribo, commented: "Ribo boasts a competitive and rich global pipeline in cardiovascular and metabolic research. The collaboration with Qilu, whose capabilities in drug translation and commercialization are exceptional, gives us confidence that our joint efforts will dramatically quicken the development and commercialization of RBD7022, bringing novel oligonucleotide therapeutic approaches to Chinese patients in the near future."

On December 22, 2023 (the "Closing Date"), LianBio Development (HK) Limited ("LianBio Development"), a subsidiary of LianBio, Janssen Pharmaceutica NV ("Janssen"), a Johnson & Johnson company, and, as applicable, LianBio reported to have entered into an Asset Purchase Agreement (the "APA"). LianBio Development and LianBio had previously entered into a License, Development and Commercialization Agreement, dated as of May 11, 2021, as amended by that certain Amendment No. 1 thereto dated March 16, 2023 (the "Lian LDCA") with Nanobiotix S.A. ("Nanobiotix"), pursuant to which Nanobiotix granted to LianBio Development certain rights and licenses to develop and commercialize NBTXR3, an investigational potential first-in-class radioenhancer, in Mainland China, Hong Kong, Taiwan, Macau, South Korea, Singapore and Thailand (Filing, 8-K, LianBio, DEC 22, 2023, View Source [SID1234638795]). Under the APA, LianBio Development and certain of its affiliates (the "Seller Entities") will sell to Janssen all of the Seller Entities’ rights, tile and interests in the products licensed to LianBio Development under the Lian LDCA (the "Licensed Products") along with certain related properties and assets, and Janssen will assume certain related liabilities, each effective as of the Closing Date. The transactions contemplated by the APA and related ancillary documents are hereinafter referred to as the "Transactions."

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Pursuant to the APA, LianBio Development will receive a one-time payment of $25 million. In addition, LianBio Development is eligible to receive a sales milestone payment of $5 million within 60 days after the end of the first calendar year in which the aggregate net sales of the Licensed Products in the People’s Republic of China exceed $20 million.

In addition, LianBio Development will perform certain transition activities to facilitate the transition of development of the Licensed Products and the related properties and assets, including the transfer of certain regulatory approvals, filings and studies as well as certain ongoing regulatory activities related to the Licensed Products and the related properties and assets during the transition period, as applicable. The transition activities are expected to be completed within six months following the Closing Date.

Concurrently with the execution of the APA, LianBio, LianBio Development, Nanobiotix and Janssen entered into a Novation Agreement, dated as of December 22, 2023, pursuant to which Nanobiotix acknowledged and consented to the Transactions, including the novation and assumption or termination of LianBio Development’s right, title and interest in the Lian LDCA and any other contracts which Janssen will assume to which Nanobiotix or any of its affiliates is a party.

The foregoing description of the APA is qualified in its entirety by reference to the full text of the APA, a copy of which LianBio expects to include as an exhibit to a future periodic report, to be filed with the U.S. Securities and Exchange Commission.

On December 22, 2023 CEL-SCI Corporation (NYSE American: CVM) reported financial results for the fiscal year ended September 30, 2023, as well as key clinical and corporate developments (Press release, Cel-Sci, DEC 22, 2023, View Source [SID1234638785]).

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Clinical and Corporate Developments:

CEL-SCI identified the target head and neck cancer patient population for Multikine that will be the basis for the Company’s regulatory filings for marketing clearance. The new data were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress. The target population, which saw its 5-year risk of death cut in half, can be identified prior to surgery upon diagnosis with tests that physicians routinely use in cancer screenings, a key finding for Multikine, which is a neoadjuvant therapy. A summary of Multikine’s results in the target population include the following:
73% survival for Multikine vs 45% in the control at 5 years
28% absolute survival benefit
Statistically significant p = 0.0015 and hazard ratio = 0.35
Tumor reduction rate >13% and tumor downstaging >35%
No safety signals or toxicities vs standard of care
Target population of an estimated 145,000 patients (global, annual) who present with:
No nodal involvement and no extracapsular spread
Low PD-L1 tumor expression (different from high PD-L1 targeted by checkpoint inhibitors)
Physicians routinely assess these features at baseline; no extra tests needed
These features make it easy to write a label for Multikine, which is essential for drug approval
Marking a major milestone toward regulatory approval, the UK’s National Institute for Health and Care Excellence (NICE) selected Multikine to be evaluated as the potential new standard of care for squamous cell carcinoma of the head and neck (SCCHN). NICE posted a detailed report from the UK’s National Institute for Health and Care Research (NIHR) regarding Multikine, its clinical data, and its potential to become a better standard of care in treating newly diagnosed head and neck cancer in the UK. This published report informs UK doctors, patients, and other interested parties that NICE has started the review of Multikine and is soliciting public comment. CEL-SCI has submitted its SCCHN target population data to the UK’s health regulator, the Medicines and Healthcare Products Regulatory Agency, and is anticipating a Scientific Advise meeting in H1 2024.
CEL-SCI expects to submit the target population data to the U.S. Food and Drug Administration (FDA) and Health Canada in Q1 2024. Health Canada advised CEL-SCI to request advance consideration for approval under a Notice of Compliance with Conditions policy which could lead to commercialization as early as 2024 if approved. The target population data have also been submitted to the European Medicines Agency (EMA) with a Scientific Advise Meeting expected H1 2024.
Additional results from the Phase 3 clinical trial of Multikine in advanced primary head and neck cancer were presented at the following conferences:
10th European Congress on Head & Neck Oncology (ECHNO) 2023
"Leukocyte Interleukin Injection (LI) immunotherapy followed by radiotherapy extends overall survival (OS) in treatment naïve locally advanced primary squamous cell carcinoma of the head & neck: the IT-MATTERS Study" (Link to data)
European Society for Radiotherapy and Oncology (ESTRO) 2023
"Histopathology population (HPP) confirms Multikine* [Leukocyte Interleukin Injection (LI)] treatment (Tx) outcome in naïve locally advanced primary head & neck squamous cell carcinoma SCCHN)" (Link to data)
American Head and Neck Cancer Society’s (AHNS) 11th Annual International Conference on Head and Neck Cancer 2023
"Tumor cell PD-L1 biomarker confirms Leukocyte Interleukin Injection (LI) treatment (Tx) survival outcome advantage in naive locally advanced primary head & neck squamous cell carcinoma (SCCHN), the IT-MATTERS Study" (Link to data)
European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress 2023
"Early response to Neoadjuvant Leukocyte Interleukin Injection (LI) immunotherapy extends overall survival (OS) in locally advanced primary squamous cell carcinoma (SCC) of the head & neck (HN): the IT-MATTERS Study" (Link to data)
New PD-L1 biomarker findings from the Phase 3 study, which have been integrated into the new target population, were presented at AHNS. The new data demonstrated that Multikine significantly increases overall survival in patients with low levels of tumor cell PD-L1 expression in contrast to approved checkpoint inhibitors, such as Keytruda and Opdivo, which most often show longer survival in a proportion of patients with a higher level of tumor cell PD-L1 expression, suggesting a combination therapy could boost patient outcomes. CEL-SCI filed a patent for the use of Multikine in tumors expressing low levels of PD-L1.
CEL-SCI’s cGMP state-of-the-art dedicated manufacturing facility commissioning is substantially complete, a significant milestone toward a planned Biologics License Application (BLA) with several regulatory agencies for approval of Multikine.
"The identification of our target patient population is a tremendous achievement that we accomplished in conjunction with regulators and the top key opinion leaders in head and neck cancer, backed by our Phase 3 data from the largest study of its kind in the world. Based on these findings, Multikine’s approval pathway focuses on the 70% of patients not well served by the two leading approved head and neck cancer drugs, Keytruda and Opdivo, which are not approved as pre-surgical treatments, CEL-SCI’s intended market," stated CEL-SCI CEO, Geert Kersten. "We are working diligently to move forward on the regulatory front, with several meetings and filing upcoming next year."

Financial Results

During the year ended September 30, 2023, research and development expenses were $22.5 million, a decrease of approximately $2.9 million, or 11%, from $25.4 million in the prior fiscal year. General and administrative expenses in fiscal 2023 were $9 million, a decrease of approximately $1.7 million, or 16%, compared to the year ended September 30, 2022. Net loss narrowed by $4.5 million, or 12%, to approximately $32.2 million for the twelve months ended September 30, 2023 from $36.7 million in fiscal 2022. Almost 40% of the loss is non-cash expenditures. CEL-SCI’s audited financial statements contained an audit opinion from its independent registered public accounting firm that included an explanatory paragraph related to CEL-SCI’s ability to continue as a going concern.