On December 26, 2023 Bristol Myers Squibb (NYSE: BMY) and RayzeBio, Inc. (NASDAQ: RYZB) reported a definitive merger agreement under which Bristol Myers Squibb will acquire RayzeBio for $62.50 per share in cash, for a total equity value of approximately $4.1 billion, or $3.6 billion net of estimated cash acquired (Press release, Bristol-Myers Squibb, DEC 26, 2023, View Source [SID1234638794]). The transaction was unanimously approved by both the Bristol Myers Squibb and RayzeBio Boards of Directors.

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RayzeBio is a clinical-stage radiopharmaceutical therapeutics ("RPT") company with an innovation-leading position in actinium-based RPTs and a pipeline of potentially first-in-class and best-in-class drug development programs. Current pipeline programs are targeting the treatment of solid tumors, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), small cell lung cancer, hepatocellular carcinoma and other cancers. There remains a high, unmet need for more effective treatments in solid tumors, and RPTs enable a precision approach to patient treatment. RPTs bind to tumor cells and deliver targeted radiation to induce cancer cell death. Actinium-based RPTs offer potential advantages over currently available RPTs since the high potency and short firing range of the alpha-emitter create the possibility for stronger efficacy and more targeted delivery.

"This transaction enhances our increasingly diversified oncology portfolio by bringing a differentiated platform and pipeline, and further strengthens our growth opportunities in the back half of the decade and beyond," said Christopher Boerner, Ph.D., Chief Executive Officer of Bristol Myers Squibb. "Radiopharmaceutical therapeutics are already transforming cancer care, and RayzeBio is at the forefront of pioneering the application of this novel modality. We look forward to supporting and accelerating RayzeBio’s preclinical and clinical programs and advancing its highly innovative radiopharmaceutical platform."

"Acquiring RayzeBio’s differentiated actinium-based radiopharmaceutical platform will establish Bristol Myers Squibb’s presence in one of the most promising and fastest-growing new modalities for the treatment of patients with solid tumors – delivering radioactive payloads to cancer cells in a targeted manner," said Samit Hirawat, M.D., Executive Vice President, Chief Medical Officer, Drug Development of Bristol Myers Squibb. "In addition, RayzeBio’s platform has the potential to be a significant IND engine, generating several therapeutic candidates in the future by leveraging our global drug development capabilities and infrastructure."

Ken Song, M.D., President and CEO of RayzeBio, said, "Despite therapeutic advances in recent years, the need for more effective treatments in solid tumors persists, and radiopharmaceutical therapeutics are positioned to be an important next wave of innovation in oncology therapy. Bristol Myers Squibb’s well-established presence in oncology and deep expertise in developing, commercializing and manufacturing treatments on a global scale makes it the ideal partner for RayzeBio at this important moment in our evolution. I am excited to see what our team achieves as part of Bristol Myers Squibb."

RayzeBio’s portfolio includes:

Lead program RYZ101 (225Ac-DOTATATE), targeting somatostatin receptor 2 (SSTR2), which is over-expressed in GEP-NETs and extensive stage small cell lung cancer (ES-SCLC). A Phase 3 clinical trial is currently enrolling patients to evaluate RYZ101 in patients with SSTR-positive GEP-NETs who have previously been treated with lutetium-177 based somatostatin therapies. RayzeBio previously reported the interim results of the Phase 1b portion of the ACTION-1 clinical trial, suggesting encouraging efficacy and tolerability. A Phase 1b clinical trial is also currently enrolling patients to evaluate RYZ101 as a first-line treatment of ES-SCLC in combination with standard-of-care therapy.
RYZ801, RayzeBio’s novel proprietary peptide targeting glypican-3 (GPC3) for delivery of actinium- based radioactivity for the treatment of hepatocellular carcinoma (HCC). RYZ801 is currently in IND-enabling studies.
Pipeline also includes an asset targeting CA9, which is expressed in renal cell cancer and is currently in IND-enabling studies.
Multiple first-in-class preclinical assets to treat solid tumors.
RayzeBio is completing construction of a state-of-the-art in-house manufacturing facility in Indianapolis, Indiana, and GMP drug production is expected to begin in the first half of 2024.

The transaction is expected to be treated as a business combination and to be dilutive to Bristol Myers Squibb’s non-GAAP diluted earnings per share by approximately $0.13 in 2024. Bristol Myers Squibb expects to finance the acquisition with primarily new debt issuance. Bristol Myers Squibb’s cash flows and strong financial profile enable continued commitment to strong investment-grade credit ratings and investment for growth through business development opportunities and distributions to shareholders through ongoing dividends and share repurchases.

Transaction Terms and Financing

Under the terms of the merger agreement, Bristol Myers Squibb will promptly commence a tender offer to acquire all of the outstanding shares of RayzeBio common stock at a price of $62.50 per share in an all-cash transaction for a total equity value of approximately $4.1 billion, or $3.6 billion net of estimated cash acquired. RayzeBio’s Board of Directors unanimously recommends that RayzeBio’s shareholders tender their shares in the tender offer.

The transaction is expected to close in the first half of 2024, subject to customary closing conditions, including the tender of a majority of the outstanding shares of RayzeBio’s common stock and the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976. Following the successful closing of the tender offer, Bristol Myers Squibb will acquire all remaining shares of RayzeBio that are not tendered into the tender offer through a second-step merger at the same price of $62.50 per share.

Advisors

BofA Securities, Inc., is serving as financial advisor to Bristol Myers Squibb, and Covington & Burling LLP is serving as legal counsel. Centerview Partners LLC is serving as financial advisor to RayzeBio, and Cooley LLP is serving as legal counsel.

On December 26, 2023 Axcynsis Therapeutics reported that it is presenting at Biotech Showcase 2024 (Press release, Axcynsis Therapeutics, DEC 26, 2023, View Source [SID1234638793]). This year, registered attendees can view Axcynsis Therapeutics’ presentation live and access a recorded version beginning November 27th – SIX weeks before the event. With 24×7 on-demand access, attendees can view recorded presentations at their convenience when scheduling does not allow viewing during the main event week.

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Dr. Bin Zou will be presenting Axcynsis Therapeutics at the Biotech Showcase.

January 8th, 2024, at 2:45 pm Pacific time

Axcynsis Therapeutics is at the forefront of developing cutting-edge Antibody Drug Conjugate (ADC) therapies. It proudly announced its participation in the Biotech Showcase on January 8th, 2024, in San Francisco.

"We are honored to be presenting at the Biotech Showcase. Axcynsis Therapeutics is dedicated to developing the next generation of ADC platforms and drug candidates, and Axcynsis is uniquely positioned to tackle the substantial and urgent unmet needs in cancer therapeutics."

Biotech Showcase, produced by Demy-Colton and EBD Group, is an investor conference focused on driving advances in therapeutic development by providing a sophisticated networking platform for executives and investors that fosters investment and partnership opportunities. The conference takes place each year in San Francisco during one of the industry’s largest gatherings and busiest weeks.

"We are delighted that Axcynsis Therapeutics will be joining us in San Francisco and presenting at Biotech Showcase this year," said Sara Demy, CEO of Demy-Colton. "Biotech Showcase is a prime opportunity for life science entrepreneurs and investors to come together to discover the potential of innovative technologies that will drive the future of drug discovery."

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."