On March 23, 2022 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T cell therapies for the treatment of hematologic malignancies and solid tumors, reported its 2021 Annual Results (Press release, Carsgen Therapeutics, MAR 23, 2022, View Source;products-and-technologies-301508801.html [SID1234610770]).

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Business Highlights

CARsgen pipeline
CT053: completed subject enrollment for pivotal Phase II trial in China, NDA submission expected in H1, 2022
CT053: initiated pivotal Phase 2 clinical trial in North America
CT041: initiated confirmatory Phase II clinical trial in China
CT041: was granted PRIME by the EMA, and granted RMAT by the FDA
New product candidates (e.g. CT0590, CT0180 and CT0181) advanced to clinical stage
Development of innovative technologies (e.g. LADAR)
RTP Manufacturing Facility, a cGMP manufacturing facility in the U.S., began operations
Dr. Zonghai Li, Founder, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics Holdings Limited, commented that, "This is the first Annual Results following CARsgen’s listing on the Hong Kong Stock Exchange on June 18, 2021. In the past year, CARsgen has made important progress, especially in pipeline development, technology innovation, CMC capacity expansion, business development, and strengthening our leadership team. Driven by the vision of Making Cancer Curable, we will continue to advance our product pipeline, develop innovative technologies, and consolidate our global strategy. We believe that we can bring innovative and differentiated cell therapy to cancer patients around the world as soon as possible, creating value for investors and the public."

1. Rapid progress of pipeline products

CT053

CT053 is an autologous CAR T-cell product candidate against BCMA being developed for the treatment of relapsed/refractory multiple myeloma (R/R MM). It incorporates a CAR construct engineered by CARsgen that features a fully human BCMA-specific single-chain variable fragment with lower immunogenicity and increased stability, which reduces the self-activation of CAR T-cells in the absence of tumor associated targets.

CARsgen has completed subject enrollment in the pivotal Phase II trial in China (LUMMICAR STUDY 1). In addition, CARsgen has started the pivotal Phase 2 clinical trial in North America (LUMMICAR STUDY 2) and treated the first subject in the pivotal Phase 2 trial in August 2021. As communicated with the U.S. FDA, the company is adding outpatient administration of CT053 into its U.S. clinical investigations.

CARsgen plans to make regulatory submissions for marketing approval to the NMPA in the first half of 2022 and plans to submit the BLA to the U.S. FDA in 2023. The company also plans to conduct additional clinical trials to develop CT053 as an earlier line of treatment for multiple myeloma.

Additional data update from the Phase I/II study in China (LUMMICAR STUDY 1) and an integrated analysis in participants with R/R MM by high-risk factors have been available as posters at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) ("ASH") Annual Meeting in December 2021.

CT041

CT041 is an autologous CAR T-cell product candidate against the protein Claudin18.2 (CLDN18.2) and has the potential to be first-in-class globally. CT041 targets the treatment of CLDN18.2 positive solid tumors with a primary focus on gastric/gastroesophageal junction cancer (GC/GEJ) and pancreatic cancer (PC). In addition to the investigator-initiated trials, CARsgen has initiated a Phase Ib clinical trial for advanced GC/GEJ and PC and a confirmatory Phase II clinical trial for advanced GC/GEJ in China, and initiated a Phase 1b clinical trial for advanced gastric or pancreatic adenocarcinoma in North America.

In North America, CARsgen has initiated the Phase 1b trial of CT041-ST-02 and has treated the first subject in July 2021.

In 2020 and 2021, CT041 received Orphan Drug designation from the U.S. FDA for the treatment of GC/GEJ and Orphan Medicinal Product designation from the EMA for the treatment of advanced gastric cancer. In November 2021, CT041 was granted PRIME eligibility by the EMA for the treatment of advanced gastric cancer. In January 2022, CT041 was granted Regenerative Medicine Advanced Therapy (RMAT) Designation for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma with CLDN18.2 positive tumors.

CARsgen plans to submit an NDA to the NMPA in China in the first half of 2024 and also plans to initiate a Phase 2 clinical trial in the second half of 2022 in North America and to submit the BLA to the U.S. FDA in 2024.

CT041 has demonstrated promising therapeutic efficacy and safety in the ongoing investigator-initiated trial. The updates on the investigator-initiated trial of CT041 have been presented at the European Society for Medical Oncology Congress 2021 ("ESMO Congress 2021").

CT011

CT011 is an autologous CAR T-cell product candidate with proof-of-concept clinical data for the treatment of hepatocellular carcinoma (HCC) and has the potential to be the first-in class globally. The company has completed enrollment of a Phase I trial in China.

CT032

CT032 is an autologous CAR T-cell product candidate against CD19 being developed for the treatment of B cell Non-Hodgkin’s lymphoma (NHL). The company is conducting a Phase I/II clinical trial in China.

AB011

AB011 is a humanized monoclonal antibody product candidate against CLDN18.2 being developed for the treatment of CLDN18.2 positive solid tumors. During the second quarter 2021, CARsgen received supplemental application approval by CDE regarding the addition of a chemotherapy combination cohort with AB011 in Phase Ib, and the company has subsequently initiated the combination cohort of AB011 with chemotherapy. The company completed Phase I monotherapy cohort enrollment and initiated combination with chemotherapy.

The company plans to consult with the NMPA in the second half of 2022 and to initiate the subsequent Phase II clinical trial.

CT0180

CT0180 is an autologous T cell product engineered to express a fusion protein of GPC3-targeted antibody fused T cell receptor (aTCR). Preclinical studies have shown that CT0180 could effectively recognize and kill GPC3-positive hepatocellular carcinoma cells and significantly inhibit HCC tumor growth in mouse xenograft models with reduced cytokine release compared to GPC3-CAR T-cells in vitro and in vivo, which improve the safety and applicability of adoptive cell therapies.

CT0181

CT0181 is an autologous T cell product engineered with GPC3-targeted antibody fused T cell receptor co-expressing IL-7 cytokine. Preclinical studies have shown that CT0181 displays superior antitumor efficacy, T cell persistence, and immunological memory in solid tumors xenografts with low cytokine release compared to GPC3-CAR T-cells.

KJ-C2111 (CT0590)

CT0590 is an allogeneic CAR T-cell product candidate deploying THANK-uCAR technology that targets BCMA. CARsgen is developing CT0590 for the treatment of relapsed/refractory multiple myeloma (R/R MM). The company has initiated IIT trial to evaluate the efficacy and safety of CT0590 for the treatment of R/R MM.

In addition, there are other IND-enabling or pre-clinical stage product candidates: KJ-C1807 (CT048), KJ-C2112, KJ-C2113 and KJ-C2114.

2. Continuous Discovery and Technology Development

Despite the approved CAR T-cell products for the treatment of terminal line hematologic malignancies, there are still significant challenges. CARsgen strives to explore and develop innovative technology platforms to address these challenges to generate better cell therapy products to global cancer patients. The main focus includes:

Increasing efficacy against solid tumors: developing innovative technologies, such as CycloCAR technology, to enhance efficacies of CAR T-cell against solid tumors. CycloCAR is a next generation CAR T technology, which co-expresses cytokine IL-7 and chemokine CCL21 and potentially has greater clinical efficacy and reduced requirement for lymphodepletion conditioning.
Enhancing safety profile: developing innovative technologies to minimize safety concerns including CRS/neurotoxicity/on-target off-tumor toxicities.
Expanding patient accessibility: advancing differentiated allogeneic THANK-uCAR technology to reduce costs and increase affordability. THANK-uCAR technology has the potential to overcome inefficient expansion and persistence associated with existing universal CAR T-cells.
Improving target availability: exploring innovative technologies that can potentially enhance drug target availability and specificity of CAR T-cell therapy. CARsgen has developed Local Action Driven by Artificial Receptor (LADAR) technology, in which the intracellular transcription of the gene of interest is controlled by a chimeric regulatory antigen receptor. Through the LADAR artificial receptor, the intracellular activity is only triggered when the extracellular domain is activated upon binding to specific antigen, making it possible to precisely control when and where immune cells act against cancer cells.
These technologies are currently being developed in-house with global rights and can be used alone or combined to upgrade CARsgen’s existing product candidates as well as to generate future innovative pipeline product candidates.

As of December 31, 2021, CARsgen had more than 300 patents of which more than 60 patents had been issued globally including China, the United States, Europe, and Japan.

3. Manufacturing Capacity Expansion

CARsgen has established in-house end-to-end clinical and commercial manufacturing capabilities for all three stages of CAR T manufacturing, including production of plasmids, lentiviral vectors, and CAR T-cells. With the clinical manufacturing facility in Xuhui, Shanghai and commercial GMP manufacturing facility in Jinshan, Shanghai, CARsgen has been manufacturing CAR T-cells in house to support clinical trials in China and manufacturing the lentiviral vectors in house to support clinical trials globally.

The company has been expanding manufacturing capacity in China and the U.S. to support both the clinical trials and the subsequent commercialization of pipeline products. The company has opened its CGMP manufacturing facility located at the Research Triangle Park (RTP) in Durham, North Carolina ("The RTP Manufacturing Facility"). The RTP Manufacturing Facility, with a total gross floor area of approximately 3,300 sq.m, will provide additional manufacturing capacity of autologous CAR T-cell products for 700 patients annually, and it will support the company’s ongoing clinical studies and early commercial launch in North America and Europe.

4. External License Agreement

CAFA Therapeutics, a subsidiary of CARsgen Therapeutics, has entered into a licensing agreement with HK inno.N Corporation (KOSDAQ: 195940) to develop and commercialize CT032 and CT053, for the potential treatment of various cancers in the Republic of Korea, with an upfront and additional milestone payments totaling up to USD50 million plus up to double-digit percentage royalties on net sales. The collaboration with HK inno.N showcases CARsgen’s commitment to establishing more external partnerships with leading pharmaceutical companies to maximize the application of its technology platform and the value of its product pipeline to benefit more cancer patients globally.

On March 23, 2022 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T cell therapies for the treatment of hematologic malignancies and solid tumors, reported that CT041, an autologous CAR T-cell product candidate against the protein Claudin18.2 (CLDN18.2), has completed the first patient enrollment in the confirmatory Phase II clinical trial in Beijing Cancer Hospital in China for the treatment of CLDN18.2 positive advanced gastric/gastroesophageal junction cancer (GC/GEJ) in patients who have failed at least 2 prior lines of therapies (Press release, Carsgen Therapeutics, MAR 23, 2022, View Source [SID1234610769]).

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Dr. Zonghai Li, Founder, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics Holdings Limited, commented that, "The IIT data disclosed at the ESMO (Free ESMO Whitepaper) in September 2021 have shown promising efficacy and safety of CT041. In the following clinical trials, we will further explore the efficacy and safety of CT041 in the treatment of advanced gastric/gastroesophageal junction cancer, as well as pancreatic cancer. We hope that CT041, a potential first-in-class CAR T-cell therapy, could make considerable progress and meet the unmet medical needs as soon as possible."

About CT041

CT041 is an autologous CAR T-cell product candidate against the protein CLDN18.2 that has the potential to be the first-in-class globally. CT041 targets the treatment of CLDN18.2 positive solid tumors with a primary focus on GC/GEJ and pancreatic cancer (PC). CT041 has demonstrated promising therapeutic efficacy and favorable safety in ongoing clinical trials. CT041 has the potential to become a backbone therapy for GC/GEJ and PC in the future and benefit a large population of patients worldwide.

As of the date of the announcement, CT041 is the only CLDN18.2-targeted CAR T-cell product candidate globally that is being studied in clinical trials with IND/CTA approvals from the FDA, the NMPA, and Health Canada. In addition to the investigator-initiated trials in China, CARsgen has initiated a Phase Ib clinical trial for advanced GC/GEJ and PC, a confirmatory Phase II clinical trial for advanced GC/GEJ in China and initiated a Phase 1b clinical trial for advanced gastric or pancreatic adenocarcinoma in North America. In 2020 and 2021, CT041 received Orphan Drug designation from the U.S. FDA for the treatment of GC/GEJ and Orphan Medicinal Product designation from the EMA for the treatment of advanced gastric cancer. In November 2021, CT041 was granted PRIME Eligibility by the EMA for the treatment of advanced gastric cancer. In January 2022, CT041 was granted Regenerative Medicine Advanced Therapy (RMAT) Designation by the U.S. FDA for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma with CLDN18.2 positive tumors. CARsgen also intends to conduct a pivotal Phase 2 clinical trial in North America in 2022.

On March 23, 2022 Virtuoso Therapeutics, Inc., a private oncology-focused company developing novel bispecific antibody and antibody drug conjugate (ADC) therapies, reported that it will present two posters highlighting the preclinical data from leading bispecific antibody programs at the American Associate for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting (Press release, Virtuoso Therapeutics, MAR 23, 2022, View Source [SID1234610768]).

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The details of the Company’s presentations at the AACR (Free AACR Whitepaper) are as follows:

Poster Presentation #5385:

Title: Multiple modes of action of the CD38 x ICAM-1 bispecific antibody
Session Category: Experimental and Molecular Therapeutics
Session Title: Mechanisms of Drug Action
Presenting Author: Xiaocheng Chen, Ph.D. VP of Antibody Therapeutics
Date/Time: Friday, April 8, 2022, 12:00 – 1:00 p.m. Central
Location: E-Poster Website

Poster Presentation #3430:

Title: CD47 x ICAM-1 bispecific antibody represents a novel approach for treating ICAM-1 overexpressing tumors
Session Category: Clinical Research Excluding Trials
Session Title: Combination Immunotherapies / Therapeutic Antibodies
Presenting Author: Xinhua Wang, Ph.D. Director of Antibody Engineering
Date/Time: Tuesday, April 12, 2022, 1:30 – 5:00 p.m. Central
Location: E-Poster Website

Virtuoso bispecific antibodies confer greater tumor selectivity than monoclonal antibodies. This greater selectivity allows enhanced efficacy with strong effector functions, and improved safety profile. Posters will be available at www.virtuosotherapuetics.com after the meeting.

On March 23, 2022 Recursion (Nasdaq: RXRX), the clinical-stage biotechnology company industrializing drug discovery by decoding biology, reported business updates and financial results for its fourth quarter and fiscal year ending December 31, 2021 (Press release, Recursion Pharmaceuticals, MAR 23, 2022, View Source [SID1234610767]).

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Recursion Pipeline Programs
"2021 was an exciting year for Recursion, in which we closed one of the largest biotechnology initial public offerings in history; expanded our partnership with Bayer; entered into a transformational partnership with Roche and Genentech; received Fast Track and Orphan Drug Designations from the FDA for our NF2 and FAP programs, respectively; readied several programs to initiate clinical trials; expanded our therapeutics pipeline with numerous programs in oncology; and built and began to utilize our supercomputer, BioHive1," said Recursion Co-Founder & CEO Chris Gibson, Ph.D. "As we applied our mapping and navigating capabilities to explore complex biology, we discovered and advanced many new scientific and business opportunities. We are excited for 2022 as we work to transition more biology and chemistry from maps to medicines."

Summary of Business Highlights

Clinical Programs
Cerebral cavernous malformation (CCM) (REC-994): In March 2022, we enrolled the first patient in our Phase 2 SYCAMORE clinical trial, which is a double-blind, placebo-controlled safety, tolerability and exploratory efficacy study of this drug candidate in 60 subjects with CCM.
Neurofibromatosis type 2 (NF2) (REC-2282): We plan to initiate our Phase 2/3 POPLAR-NF2 clinical trial, which is a parallel group, two stage, randomized, multicenter study of this drug candidate in the second quarter of 2022.
Familial adenomatous polyposis (FAP) (REC-4881): We plan to initiate a Phase 2, randomized, double-blind, placebo-controlled study to evaluate safety, pharmacokinetics and efficacy of this drug candidate in the third quarter of 2022.
Preclinical and Discovery Programs
Clostridium difficile colitis (REC-3964): We made progress in IND-enabling studies for REC-3964 and plan to initiate a Phase 1 study in the second half of 2022.
Small molecule inhibitor of a target with a novel link to CDK12 biology: A small molecule inhibitor of a novel target not otherwise known to be related to CDK12, discovered using our next generation mapping and navigating technology, has demonstrated robust single-agent and combination activity with olaparib in an HRD-negative ovarian cancer PDX model, achieving 100% complete and durable response.
Cancer immunotherapy target ‘alpha’: We expanded the in vivo dataset of target alpha, where a small molecule inhibitor of target alpha, discovered using our next generation mapping and navigating technology, demonstrated robust combination activity with an anti-PD1 therapy in an EMT6 mouse model and achieved 80% complete response.
Oncology pipeline: We continued to make progress expanding and advancing numerous oncology programs, discovered using our next generation mapping and navigating technology, through scientific milestones including the programs mentioned above as well as programs related to immune checkpoint resistance in STK11-mutant non-small cell lung cancer, small molecule MYC inhibition, cancer immunotherapy target ‘beta,’ hepatocellular carcinoma, ovarian cancer, and other indications.
Roche-Genentech Collaboration: In early December 2021, we announced a transformational collaboration with Roche and Genentech to advance novel potential medicines in neuroscience and an indication in gastrointestinal oncology by mapping complex biology using the Recursion OS. In this collaboration, Recursion received an upfront payment of $150 million in January 2022, is eligible for milestones for map-building and data-sharing that could exceed $500M, as well as research and development, commercialization and net sales milestones on up to 40 programs that could exceed $300M per program and mid- to high-single digit tiered royalties on net sales for products commercialized from this work together.
Bayer AG Collaboration: In early December 2021, we announced the expansion of our collaboration with Bayer to include the use of Recursion’s biological mapping and navigating capabilities to discover small molecule drug candidates with the potential to treat fibrotic diseases. In this expanded collaboration, Recursion and Bayer may now work on more than a dozen programs of relevance to fibrotic diseases.
Recursion OS
Closed Loop Automated Synthesis Suite (CLASS): We began designing CLASS, our automated chemical microsynthesis system, which will further enable novel chemical formulation and profiling across our maps of biology and chemistry.
Total Observations: In the fourth quarter of 2021, we surpassed the milestone of executing 100 million total phenotypic experiments and producing 1 billion proprietary biological images.
Fourth Quarter and Fiscal Year 2021 Financial Results

Cash Position: Cash, cash equivalents, and investments were $516.6 million as of December 31, 2021, compared to $262.1 million as of December 31, 2020. This cash balance does not include the upfront payment of $150 million from entering into the Roche-Genentech collaboration in December 2021, which was received in January 2022.
Revenue: Total revenue, consisting primarily of revenue from collaborative agreements, was $2.5 million for the fourth quarter of 2021, compared to $2.7 million for the fourth quarter of 2020. Total revenue, consisting primarily of revenue from collaboration agreements, was $10.2 million for the year ended December 31, 2021, compared to $4.0 million for the year ended December 31, 2020. The increase in 2021 was due to revenue recognized from our collaboration with Bayer.
Research and Development Expenses: Research and development expenses were $48.3 million for the fourth quarter of 2021, compared to $20.7 million for the fourth quarter of 2020. Research and development expenses were $135.3 million for the year ended December 31, 2021, compared to $63.3 million for the year ended December 31, 2020. The increases in both periods in 2021 were primarily due to an increased number of experiments run on the Recursion OS, an increased number of assets being validated, and increased clinical costs of studies to progress our drug candidates.
General and Administrative Expenses: General and administrative expenses were $19.2 million for the fourth quarter of 2021, compared to $7.6 million for the fourth quarter of 2020. General and administrative expenses were $57.7 million for the year ended December 31, 2021, compared to $25.3 million for the year ended December 31, 2020. The increases in both periods in 2021 were due to the growth in size of the company’s operations, including an increase in salaries and wages of $16.4 million during the year ended December 31, 2021, equipment costs, human resources-related costs, facilities costs, and other administrative costs associated with operating as a high-growth company.
Net Loss: Net loss was $64.9 million for the fourth quarter of 2021, compared to a net loss of $25.8 million for the fourth quarter of 2020. Net loss was $186.5 million for the year ended December 31, 2021, compared to a net loss of $87.0 million for the year ended December 31, 2020.
Additional Corporate Updates

Letter to Shareholders: Recursion Co-Founder & CEO Chris Gibson, Ph.D. wrote an annual letter to shareholders which may be found in our 10-K report filed with the SEC.
Environmental, Social, and Governance (ESG) Report: Recursion has prepared a report which describes our operations in relation to a number of ESG metrics. A copy of this report may be found on the Recursion website at www.Recursion.com.
Neuroscience: Tim Ahfeldt, Ph.D. joined Recursion as Fellow, Neuroscience; Irit Rappley, Ph.D. joined Recursion as Vice President, Neuroscience and Translational Research; and Glenn Morrison, Ph.D. joined Recursion as Vice President, Clinical Development.
Clinical Development: Rogelio Mosqueda-Garcia, M.D., Ph.D. joined Recursion as Vice President, Clinical Development & Head of Human Pharmacology and Translational Medicine and Lisa Boyette, M.D., Ph.D. was promoted to Vice President, Medical Affairs.
Chemical Technology & Manufacturing: David Northrup joined Recursion as Vice President, Manufacturing & Supply Chain and Thierry Masquelin, Ph.D. joined Recursion as Senior Director, Chemical Technology.
Intellectual Property: Rich Person, J.D. joined Recursion as Vice President, Intellectual Property.
Annual Shareholder Meeting: The Recursion Annual Meeting of Shareholders will be held on June 14, 2022.

On March 23, 2022 Novartis reported that the US Food and Drug Administration (FDA) approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan) (formerly referred to as 177Lu-PSMA-617) for the treatment of adult patients with a certain type of advanced cancer called prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer (PSMA-positive mCRPC) that has spread to other parts of the body (metastatic)1 (Press release, Novartis, MAR 23, 2022, View Source [SID1234610766]). These patients have already been treated with other anti-cancer treatments (androgen receptor pathway inhibition and taxane-based chemotherapy)1.

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Experience the interactive Multichannel News Release here: View Source

"The approval of Pluvicto is an important clinical advancement for people with progressing mCRPC, as it can significantly improve survival rates for those who have limited treatment options," said Oliver Sartor, MD, Medical Director at Tulane Cancer Center. "Pluvicto is a step forward in the evolution of precision medicine for prostate cancer."

Pluvicto is the first FDA-approved targeted radioligand therapy (RLT) for eligible patients with mCRPC that combines a targeting compound (ligand) with a therapeutic radioisotope (a radioactive particle)1. Pluvicto is expected to be available to physicians and patients within weeks.

The FDA has also approved Locametz (kit for the preparation of gallium Ga 68 gozetotide injection)2. After radiolabeling, this imaging agent may be used to identify PSMA-positive lesions in adult patients with mCRPC through a positron emission tomography (PET) scan2. Gallium-68 labeled Locametz can identify tumor lesions expressing the PSMA biomarker and locate where in the body tumors may have spread (eg, in soft tissue, lymph nodes, or bone), identifying patients eligible for targeted treatment with Pluvicto1,2. PSMA is highly expressed in more than 80 percent of patients with prostate cancer, making it an important phenotypic biomarker for assessing the progression of metastatic prostate cancer10. Locametz is expected to be available to physicians and patients within weeks.

"With our unique strategy to tackle cancer by leveraging four therapeutic platforms, I am thrilled that with Pluvicto, we are bringing the targeted RLT platform to bear for treating eligible patients with mCRPC," said Susanne Schaffert, PhD, President, Novartis Oncology. "Today’s approval builds upon our history in prostate cancer, a devastating disease where we believe our innovation can make a meaningful difference to patients."

FDA approval of Pluvicto is based on the results of the Phase III VISION trial which demonstrated that PSMA-positive mCRPC patients previously treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy who received Pluvicto plus standard of care (SOC) had improved overall survival compared to SOC alone1. Participants treated with Pluvicto plus SOC had a 38% reduction in risk of death and a statistically significant reduction in the risk of radiographic disease progression or death (rPFS) compared to SOC alone1. Interpretation of the magnitude of the rPFS effect was limited due to a high degree of censoring from early drop out in the control arm1.

In addition, about a third (30%) of patients with evaluable disease at baseline demonstrated an overall response (per RECIST 1.1) with Pluvicto plus SOC, compared to 2% in the SOC alone arm1. The most common adverse events (all grades) in the Pluvicto arm of the study were fatigue (43%), dry mouth (39%), nausea (35%), anemia (low red blood cell counts) (32%), decreased appetite (21%), and constipation (20%)1.

"Prostate cancer is the second leading cause of cancer-related death in Americans with a prostate gland13. Although the treatment landscape for mCRPC continues to evolve, there is a high unmet need for additional precision medicine treatment options to improve outcomes for these patients," said Jamie Bearse, CEO and President at ZERO – The End of Prostate Cancer. "The approval of Pluvicto offers new hope to the mCRPC community."

Pluvicto and Locametz are registered products of Advanced Accelerator Applications, the radioligand business of Novartis, approved in the United States for physicians to prescribe to appropriate patients. Additional safety details for Pluvicto and Locametz, and full Prescribing Information can be found on the Novartis website.

About Pluvicto
Pluvicto (lutetium Lu 177 vipivotide tetraxetan) is indicated for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have already been treated with other anticancer treatments (androgen receptor pathway inhibition (ARPI) and taxane-based chemotherapy)1. It is a type of precision cancer treatment combining a targeting compound (ligand) with a therapeutic radioisotope (a radioactive particle)1. After administration into the bloodstream, Pluvicto binds to target cells, including prostate cancer cells that express PSMA, a transmembrane protein1. Once bound, energy emissions from the radioisotope damage the target cells and nearby cells disrupting their ability to replicate and/or triggering cell death1.

Novartis has submitted marketing authorization for Pluvicto to the European Medicines Agency and other health authorities.

About Locametz
Locametz (gallium Ga 68 gozetotide), diagnostic kit for radiopharmaceutical injectable preparation is indicated for positron emission tomography (PET) of PSMA-positive lesions with prostate cancer with suspected metastasis who are candidates for initial definitive therapy; with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level; and for selection of patients with metastatic prostate cancer, for whom lutetium Lu 177 vipivotide tetraxetan PSMA-directed therapy is indicated2.

Novartis has submitted marketing authorization for Locametz to the European Medicines Agency and other health authorities.

About VISION
VISION is an international, prospective, randomized, open-label, multicenter, phase III study that assessed the efficacy and safety of Pluvicto (lutetium Lu 177 vipivotide tetraxetan) (7.4 GBq administered by IV infusion every 6 weeks for a maximum of 6 cycles) plus investigator-chosen standard of care (SOC) in the investigational arm, versus SOC in the control arm1. Patients with PSMA PET-scan positive mCRPC who have received androgen receptor (AR) pathway inhibition and taxane-based chemotherapy were randomized in a 2:1 ratio in favor of the investigational arm1. The alternate primary endpoints were rPFS and OS1. The study enrolled 831 patients1.

About Phenotypic Precision Medicine in Advanced Prostate Cancer
Despite advances in prostate cancer care, there is a high unmet need for new targeted treatment options to improve outcomes for patients with mCRPC. More than 80% of patients with prostate cancer highly express a phenotypic biomarker9 called prostate specific membrane antigen (PSMA)4-6,9,10, making it a promising diagnostic (through positron emission tomography (PET) scan imaging) and therapeutic target for radioligand therapy10. This differs from ‘genotypic’ precision medicine which targets specific genetic alterations in cancer cells7.

Novartis and Prostate Cancer
With more 1.4 million new cases and 375,000 deaths in 2020 alone, prostate cancer is the most frequently diagnosed cancer in 112 countries—more than half the world12.

At Novartis, we are harnessing the innovation of our world-class scientists, strategic partnerships, and one of the industry’s most competitive pipelines to explore the potential of new, targeted therapies and precision medicine platforms to address the greatest unmet needs in prostate cancer.

Through the bold science of targeted therapies, our goal is to reduce the global disease burden, extend the lives of patients with prostate cancer, and elevate current standards of care.

Pluvicto Indication
PLUVICTO (lutetium Lu 177 vipivotide tetraxetan) is a radiopharmaceutical used to treat adults with an advanced cancer called prostate-specific membrane antigen–­­­­positive metastatic castration-resistant prostate cancer (PSMA-positive mCRPC) that has spread to other parts of the body (metastatic), and has already been treated with other anticancer treatments.

Pluvicto Important Safety Information
Use of PLUVICTO involves exposure to radioactivity. Long-term, accruing radiation exposure is associated with increased risk for cancer. To minimize radiation exposure to others following administration of PLUVICTO, patients are advised to limit close contact (less than 3 feet) with household contacts for 2 days or with children and pregnant women for 7 days, to refrain from sexual activity for 7 days, and to sleep in a separate bedroom from household contacts for 3 days, from children for 7 days, or from pregnant women for 15 days.

PLUVICTO may cause low level of blood cell counts. Patients should tell their doctor right away if they develop any new or worsening symptoms, including tiredness or weakness, pale skin, shortness of breath, bleeding or bruising more easily than normal or difficulty to stop bleeding, or frequent infections with signs such as fever, chills, sore throat, or mouth ulcers. PLUVICTO may also cause problems with kidneys. Patients should tell their doctor right away if they develop any new or worsening symptoms, including passing urine less often or passing much smaller amounts of urine than usual.

Before receiving PLUVICTO, patients should tell their doctor if they have low level of blood cell counts (hemoglobin, white blood cell count, absolute neutrophil count, platelet count); if they have or have had tiredness, weakness, pale skin, shortness of breath, bleeding or bruising more easily than normal or difficulty stopping bleeding, or frequent infections with signs such as fever, chills, sore throat, or mouth ulcers (possible signs of myelosuppression); if they have or have had kidney problems; if they have or have had any other type of cancer or treatment for cancer, as PLUVICTO contributes to long-term cumulative radiation exposure; and if they are sexually active, as all radiopharmaceuticals, including PLUVICTO, have the potential to cause harm to an unborn baby. Patients should use effective contraception for intercourse during treatment with PLUVICTO and for 14 weeks after the last dose. PLUVICTO may cause temporary or permanent infertility.

Before administration of PLUVICTO patients should drink plenty of water in order to urinate as often as possible during the first hours after administration.

The most common side effects of PLUVICTO include tiredness, dry mouth, nausea, low red blood cell count, loss of appetite, changes in bowel movements (constipation or diarrhea), vomiting, low blood platelet count, urinary tract infection, weight loss, and abdominal pain.

Please see full Prescribing Information for PLUVICTO at View Source

Locametz Indication
LOCAMETZ (kit for the preparation of gallium Ga 68 gozetotide injection), after radiolabeling with gallium-68, is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA)-positive lesions in men with prostate cancer:

with suspected metastasis who are candidates for initial definitive therapy
with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level
for selection of patients with metastatic prostate cancer for whom lutetium Lu 177 vipivotide tetraxetan PSMA-directed therapy is indicated
Locametz Important Safety Information
LOCAMETZ PET images can be misinterpreted. Gallium Ga 68 gozetotide may be taken up into other types of cancerous and noncancerous tissue. Corroborating approaches, which may include histopathology, are recommended.

Gallium Ga 68 gozetotide contributes to a patient’s long-term cumulative radiation exposure, which is associated with an increased risk of cancer. Safe handling and preparation procedures must be ensured to protect patients and health care workers from unintentional radiation exposure. Patients should be well hydrated prior to administration and urinate immediately prior to and frequently during the first hours after image acquisition to reduce radiation exposure.

Adverse reactions that occurred at a rate of 0.5% or greater in the VISION study were fatigue, nausea, constipation, and vomiting; at a rate less than 0.5%, diarrhea, dry mouth, injection site reactions, and chills.

Please see full Prescribing Information for LOCAMETZ at View Source

Patient Access and Support
Novartis is committed to helping ensure that our medicines are accessible to as many patients as possible. With the approval of Pluvicto in the United States, we offer support and services to address a range of needs through AAA PatientCONNECT. AAA PatientCONNECT is a support center staffed by dedicated case managers who can help eligible patients throughout their treatment journey to start and stay on treatment. Patients or providers can call 1-844-638-7222 or visit AAApatientconnect.com to enroll and learn more about AAA PatientCONNECT.