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.

On December 22, 2023 Clarity Pharmaceuticals (ASX: CU6) ("Clarity"), a clinical stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported that the first patient has been dosed in its pivotal Phase III 64Cu-SAR-bisPSMA diagnostic trial in prostate cancer, CLARIFY (NCT06056830)1, at the Urology Cancer Center / XCancer Omaha, NE (Press release, Clarity Pharmaceuticals, DEC 22, 2023, View Source [SID1234638784]).

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The aim of the CLARIFY study is to assess the diagnostic performance of 64Cu-SAR-bisPSMA to detect regional nodal metastases in participants with high-risk prostate cancer prior to radical prostatectomy. The study will recruit 383 participants at multiple clinical sites across the United States and Australia.

Evaluation of the first patient is taking place over 2 imaging timepoints, day 1 (day of administration) and day 2 (approximately 24 hours post administration) and the patient will be followed up as per protocol. Subsequent patients will be evaluated in the same manner. As a pivotal trial, the final study results are intended to provide sufficient evidence to support an application to the FDA for approval of 64Cu-SAR-bisPSMA as a new diagnostic imaging agent in prostate cancer in pre-prostatectomy patients.

Clarity’s Executive Chairperson, Dr Alan Taylor, commented, "We are excited to have successfully dosed the first participant in the CLARIFY trial with our optimised SAR-bisPSMA agent. The trial is driven by the compelling findings from our PROPELLER trial (NCT04839367)2,3 which highlighted the robust safety profile and superior performance of 64Cu-SAR-bisPSMA compared to standard of care imaging (68Ga-PSMA-11) with imaging on the day of administration, with two to three times the amount of product taken up in the lesions2,3. The longer half-life of copper-64 based diagnostics, in comparison to the currently used gallium-68 and fluorine-18 based products, also allows for delayed imaging. These unique features have the potential to enable detection of additional lesions compared to standard of care imaging and may address the significant shortfall in sensitivity of these agents. Additionally, the extended shelf-life of 64Cu-SAR-bisPSMA of up to 48 hours, in contrast to the short shelf-life of currently available PSMA PET tracers, not only enhances scheduling flexibility for clinics, but also addresses a critical need for diagnostics in geographic areas with limited access to the current generation of radiopharmaceuticals.

"Clarity is steadfast in addressing the high unmet need for diagnostics and therapies in the prostate cancer domain. Our optimism is rooted in the belief that our SAR-bisPSMA product can redefine diagnostic standards and improve patient outcomes. As we progress with the CLARIFY trial, we anticipate validating and building upon the positive data accumulated so far. Our vision is a future where enhanced diagnostic tools empower clinicians to make more informed decisions, ultimately shaping the optimal course of treatment for their patients.

"Although the current generation of PSMA-based radiopharmaceuticals is broadening the horizons of prostate cancer management and offering new treatment pathways for patients in need, we have seen in Clarity’s PROPELLER trial that 64Cu-SAR-bisPSMA has the potential of really changing this paradigm and outcomes for patients. We look forward to exploring and confirming these benefits in the CLARIFY trial."

About the CLARIFY trial

CLARIFY derives from "Positron Emission Tomography using 64Cu-SAR-bisPSMA in participants with high-risk PC prior to radical prostatectomy: A prospective, single-arm, multi-centre, blinded-review, Phase III diagnostic performance study". It is a non-randomised, open-label clinical trial in 383 participants. The primary aim of the Phase III trial is to assess the diagnostic performance of 64Cu-SAR-bisPSMA PET to detect regional nodal metastases. Furthermore, the safety, tolerability, and consistency of 64Cu-SAR-bisPSMA will be assessed. All patients will receive a single administration of 200MBq 64Cu-SAR-bisPSMA. Evaluation will take place over 2 imaging timepoints, Day 1 (day of administration) and Day 2 (approximately 24 hours post administration).

About SAR-bisPSMA

SAR-bisPSMA derives its name from the word "bis", which reflects a novel approach of connecting two PSMA-targeting agents to Clarity’s proprietary sarcophagene (SAR) technology that securely holds copper isotopes inside a cage-like structure, called a chelator. Unlike other commercially available chelators, the SAR technology prevents copper leakage into the body. SAR-bisPSMA is a TCT that can be used with isotopes of copper-64 (Cu-64 or 64Cu) for imaging and copper-67 (Cu-67 or 67Cu) for therapy.

64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA are unregistered products. Individual results may not represent the overall safety and efficacy of the products. A clinical development program is currently underway to assess the efficacy and safety of these products. There is no guarantee that these products will become commercially available.

About Prostate Cancer

Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of cancer death worldwide4. The American Cancer Institute estimates in 2023 there will be 288,300 new cases of prostate cancer in the US and around 34,700 deaths from the disease.