On August 9, 2022 PMV Pharmaceuticals, Inc. ("PMV Pharma" Nasdaq: PMVP), a precision oncology company pioneering the discovery and development of small molecule, tumor-agnostic therapies targeting p53, reported financial results for the second quarter ended June 30, 2022, and provided a corporate update (Press release, PMV Pharma, AUG 9, 2022, View Source [SID1234617942]).

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"The highlight of the second quarter was the oral presentation at ASCO (Free ASCO Whitepaper) of positive initial data from the ongoing PYNNACLE study of PC14586, our investigational first-in-class p53 Y220C reactivator, in patients with solid tumors," said David Mack, Ph.D., President and Chief Executive Officer of PMV Pharma. "The data provide clinical proof of concept for PC14586 as monotherapy, with meaningful clinical activity observed across multiple tumor types."

Corporate Highlights:

Initial data from the dose-escalation portion of the Phase 1/2 PYNNACLE study were featured in an oral presentation at the 2022 ASCO (Free ASCO Whitepaper) annual meeting. Enrollment is ongoing to support the determination of a recommended Phase 2 dose.
PMV Pharma announced a clinical trial collaboration and supply agreement with Merck (known as MSD outside the U.S. and Canada) to evaluate the combination of PC14586 with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy. The combination trial is anticipated to begin in Q4 2022.
Appointed Marc Fellous, M.D. as Vice President, Clinical Development and Medical Affairs. Prior to joining PMV Pharma, Dr. Fellous was Global Medical Affairs Head on larotrectinib, the first tumor-agnostic drug approved in the U.S. and Europe, and selitrectinib programs at Bayer. He held leadership roles at Bayer and Roche for more than 13 years, contributing to the strategy and launch of multiple successful oncology products. Dr. Fellous completed his doctorate in general medicine at the University Paris V along with a specialized master’s degree in medical management from ESCP-Europe Business School.
Continued progress on the Company’s research pipeline of its Wild-Type p53-Induced Phosphatase 1 (WIP1) inhibitor and p53 mutant programs.
Second Quarter 2022 Financial Results

As of June 30, 2022, PMV Pharma had $277.4 million in cash, cash equivalents, and marketable securities, compared to $339.0 million as of June 30, 2021. Net cash used in operations was $31.7 million for the six months ended June 30, 2022, compared to $22.1 million for the six months ended June 30, 2021.
Net loss for the six months ended June 30, 2022, was $35.7 million compared to $24.5 million for the quarter ended June 30, 2021.
Research and development (R&D) expenses were $23.3 million for the six months ended June 30, 2022 compared to $15.2 million for the six months ended June 30, 2021. The increase in R&D expenses was primarily due to increased headcount and clinical trial expenses associated with advancing our lead product candidate, PC14586, through the Phase 1/2 clinical trial.
General and administrative (G&A) expenses were $13.2 million for the six months ended June 30, 2022, compared to $9.6 million for the six months ended June 30, 2021. The increase in G&A expenses was primarily due to costs relating to operating as a public company.
About PC14586
PC14586 is a first-in-class, small molecule, p53 reactivator designed to selectively bind to the crevice present in the p53 Y220C mutant protein, hence, restoring the wild-type, or normal, p53 protein structure and tumor-suppressing function. The U.S. Food and Drug Administration (FDA) granted Fast Track designation to PC14586 for the treatment of patients with locally advanced or metastatic solid tumors that have a p53 Y220C mutation. For more information about the Phase 1/2 PYNNACLE trial (PMV-586-101), refer to www.clinicaltrials.gov (NCT study identifier NCT04585750).

On August 9, 2022 Rubius Therapeutics, Inc. (Nasdaq: RUBY), a clinical-stage biopharmaceutical company that is biologically engineering red blood cells to create an entirely new class of cellular medicines called Red Cell Therapeutics for the treatment of cancer and autoimmune diseases, reported second quarter 2022 financial results and provided a business update (Press release, Rubius Therapeutics, AUG 9, 2022, View Source [SID1234617941]).

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"We continue to advance enrollment in the NSCLC and RCC expansion cohorts of our Phase 1 clinical trial of RTX-240 in combination with pembrolizumab, with initial clinical results expected in the second half of 2022, including data in advanced solid tumors and data from the initial patients with NSCLC and RCC enrolled in the study. Enrollment also progressed in the Phase 1/2 clinical trial of RTX-224 in select advanced solid tumors, with initial results expected by year-end or in the first quarter of 2023," said Pablo J. Cagnoni, M.D., president and chief executive officer. "Also, during the quarter, we presented new preclinical data, as part of our type 1 diabetes program, that demonstrated prevention of diabetes and bystander suppression in the stringent non-obese diabetes preclinical model. We plan to select a clinical candidate for our type 1 diabetes program later this year."

Recent Highlights

Oncology

RTX-240 + Pembrolizumab in Advanced Solid Tumors

RTX-240 is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to simultaneously present hundreds of thousands of copies of the costimulatory molecule 4-1BB ligand (4-1BBL) and IL-15TP (trans-presentation of IL-15 on IL-15Rα) in their native forms. RTX-240 is designed to broadly stimulate the immune system by activating and expanding both NK and CD8+ memory T cells to generate an anti-tumor response.

Advanced enrollment in the expansion cohorts of the Phase 1 combination arm of RTX-240 plus pembrolizumab in patients with advanced solid tumors
Enrolling up to 20 patients who have experienced disease progression with 1-2 prior treatment regimens in the metastatic setting in preparation for a future Phase 2 clinical trial of RTX-240 in combination with pembrolizumab in an earlier line of therapy
Initial clinical results in advanced solid tumors and data from the initial enrolled NSCLC and RCC patients expected in the second half of 2022
RTX-224

RTX-224 is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to express hundreds of thousands of copies of 4-1BBL and IL-12 on the cell surface. In contrast to RTX-240, RTX-224 is designed as a broad immune agonist of both adaptive and innate responses, activating CD8+ and CD4+ T cells, promoting antigen presentation and activating and expanding NK cells. It is expected to produce a broad and potent anti-tumor T cell response, an innate immune response and have anti-tumor activity in those tumor types with known sensitivity to T cell killing, including tumor types with high mutational burden, PD-L1 expression and prior activity of checkpoint inhibitors.

Continued dose escalation in the Phase 1/2 clinical trial of RTX-224 in select relapsed/refractory or locally advanced solid tumors, including non-small cell lung cancer, cutaneous melanoma, head and neck squamous cell carcinoma, urothelial (bladder) carcinoma and triple-negative breast cancer
Initial clinical results are expected by year-end or during the first quarter of 2023
Autoimmunity

Type 1 Diabetes

RCT product candidates are engineered to express specific autoantigens that are the target of immune responses which cause autoimmune disease. This approach takes advantage of the natural tolerogenic properties of red blood cells. RCTs are designed to suppress, modulate or eliminate disease-causing cells. Type 1 diabetes is a T-cell driven autoimmune disease with well-defined antigens, making it an ideal disease indication for this antigen-specific tolerance approach.

In June, the Company presented new preclinical data for its type 1 diabetes program at the FOCIS 2022 Annual Meeting in San Francisco:

Demonstrated tolerance induction and bystander suppression in stringent type 1 diabetes preclinical models
From ongoing experiment, showed new efficacy data in the NOD preclinical model
By increasing to 3 doses administered and optimizing the dosing schedule, bystander suppression was achieved at 25 weeks by delivering only two antigens, indicating disease prevention caused by many autoantigens
Established efficacy in the BDC2.5 adoptive transfer model with data supporting that repeated dosing extends duration of disease protection, reverses established inflammation, which is important for the treatment of existing autoimmunity, and induces two types of regulatory T cells, resulting in protection against re-challenge
These findings are potentially translatable beyond type 1 diabetes to multiple autoimmune diseases, including multiple sclerosis and celiac disease
Leadership Update

In July 2022, Rubius announced that Susanne Schaffert, Ph.D., joined its board of directors. Dr. Schaffert most recently served as President of Novartis Oncology and brings more than 25 years of experience across clinical development, marketing and sales, finance and commercialization in the global pharmaceutical and biotechnology industries, with a focus on oncology, immuno-oncology and cell therapy.

Anticipated 2022 Catalysts and Operational Objectives

To evaluate the full potential of RTX-240, Rubius’ other oncology programs and the RED PLATFORM, Rubius plans to execute several critical milestones in the near term and, based on its current cash and cash equivalents, including borrowings under its credit facility, has sufficient cash runway into the second half of 2023:

Report initial Phase 1 clinical results for RTX-240 in combination with pembrolizumab in advanced solid tumors and data from the initial enrolled NSCLC and RCC patients in the second half of 2022;
Select a clinical candidate for the first autoimmune program in type 1 diabetes during the second half of 2022; and
Report initial Phase 1 clinical results for RTX-224 for the treatment of advanced solid tumors by year-end or during the first quarter of 2023.
Second Quarter Financial Results

Net loss for the second quarter of 2022 was $44.2 million or $0.49 per common share, compared to $50.2 million or $0.56 per common share in the second quarter of 2021.

In the second quarter of 2022, Rubius invested $33.0 million in research and development (R&D) related to its novel RED PLATFORM and towards expanding and advancing its product pipeline, as compared to $36.1 million in the second quarter of 2021. The year-over-year decrease was principally due to a decrease in direct costs of $2.9 million related to the deprioritization of RTX-321 and RTX-240 AML and monotherapy studies. We expect these costs to continue to decrease in future periods. This decrease was partially offset by an increase in clinical costs related to RTX-224. Platform development, early-stage research and unallocated expenses decreased by $0.1 million primarily due to a decrease of $0.8 million in stock-based compensation expense related to a reduction in the market price of our common stock, resulting in a lower valuation of stock options granted in 2022, and a decrease of $0.3 million in facility-related and other expenses due to lower spend on non-capitalized software costs in the current year. These decreases were partially offset by an increase of $0.4 million in contract research and development related to drug discovery activities and platform development. Additionally, personnel-related costs increased by $0.5 million to support our prioritization of clinical programs.

G&A expenses were $9.9 million during the second quarter of 2022, as compared to $13.9 million for the second quarter of 2021. The lower costs were primarily due to a decrease in stock-based compensation expense of $3.7 million, which was driven by stock option awards that fully vested during the second half of 2021 and first half of 2022, as well as a reduction in the market price of our common stock, resulting in a lower valuation of stock options granted in 2022.

Six Month Financial Results

Net loss for the first six months of 2022 was $96.7 million or $1.07 per common share, compared to $92.5 million or $1.08 per common share in the first six months of 2021.

In the six months ended June 30, 2022, Rubius invested $71.3 million in R&D related to its novel RED PLATFORM and towards expanding and advancing its product pipeline, as compared to $63.7 million in the first six months of 2021. The year-over-year increase was driven primarily by an increase in direct costs of $2.1 million related to an increase in preclinical and clinical costs associated with RTX-224 and RTX-240, principally due to clinical research organization, or CRO, costs and internal manufacturing costs. This increase was partially offset by a decrease in clinical costs related to RTX-321 due to start-up activities in the prior period and current period deprioritization of clinical development. We expect these costs to decrease in future periods. Platform development, early-stage research and unallocated expenses increased by $5.4 million principally due an increase of $2.9 million in personnel-related costs related to headcount increases through the second half of 2021 to support operations. Additionally, increases of $1.7 million in contract research and development and $1.0 million in laboratory supplies and research materials were related to drug discovery activities and platform development. These increases were partially offset by a decrease of $0.4 million in facility-related and other expenses due to lower spend on non-capitalized software costs and a reduction in building operating costs in the current year.

G&A expenses were $22.5 million during the first six months of 2022, as compared to $27.1 million for the same period in 2021. The lower costs were due to a decrease in stock-based compensation expense of $5.0 million, which was driven by stock option awards that fully vested during the second half of 2021 and first half of 2022, as well as a reduction in the market price of our common stock, resulting in a lower valuation of stock options granted in 2022. The decrease was partially offset by an increase in personnel-related expenses of $0.3 million driven by additions to headcount in our general and administrative function.

Cash Position

As of June 30, 2022, cash, cash equivalents and investments were $140.7 million (including $75 million in borrowings under its credit facility), compared to $225.8 million as of December 31, 2021. During the first six months of 2022, the Company used $81.4 million of cash to fund operations, $78.4 million to purchase investments and $4.2 million to fund capital expenditures, consisting mostly of renovation costs incurred at our manufacturing facility.

On August 9, 2022 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported financial results for the second quarter ended June 30, 2022 and provided a business update (Press release, Protara Therapeutics, AUG 9, 2022, View Source [SID1234617940]).

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"We are pleased with the continued progress of the ADVANCED-1 study of TARA-002 in non-muscle invasive bladder cancer (NMIBC)," said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "We remain committed to unlocking the full potential of TARA-002 in this underserved patient population, and look forward to sharing our progress in the coming quarters. In parallel, we are keenly focused on finalizing the design of a clinical trial of TARA-002 in patients with lymphatic malformations (LMs), a rare pediatric indication for which we believe TARA-002 has the potential to serve as a much-needed intervention."

Recent Highlights

TARA-002 in NMIBC

Enrollment is progressing in the Company’s Phase 1 ADVANCED-1 clinical trial evaluating TARA-002, an investigational cell-based immunopotentiator, for the treatment of NMIBC.
In June 2022, a Trials in Progress poster related to the ADVANCED-1 Phase 1 trial was featured at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
TARA-002 in LMs

Protara continues to engage with the Vaccines and Related Products Division of the U.S. Food and Drug Administration (FDA) regarding a development path for TARA-002 in LMs. Following receipt of preliminary guidance from the FDA and in consultation with the Company’s external scientific advisory board, Protara plans to initiate a Phase 2 clinical trial of TARA-002 in LMs, subject to alignment with the agency on a trial protocol.
Protara announced that the European Medicines Agency (EMA) recently granted orphan drug designation (ODD) to TARA-002 for the treatment of LMs.
In May 2022, the Company announced results of a retrospective analysis of OK-432, the originator compound for TARA-002, for the treatment of LMs. Results from the analysis, which were presented during a poster presentation at the International Society for the Study of Vascular Anomalies World Congress 2022, showed that OK-432 met the primary efficacy endpoint of clinical success (defined as complete [90%-100%] or substantial [60%-89%] reduction in LM volume measured radiographically) in treating LMs and demonstrated a favorable safety profile.
IV Choline Chloride in Intestinal Failure Associated Liver Disease (IFALD)

The Company’s prospective study to enhance understanding of the incidence of IFALD in patients dependent on parenteral nutrition remains ongoing. Protara expects to use results from the prospective study, as well as its previously completed retrospective study, to inform next steps for the IV Choline Chloride development program.
In April 2022, the U.S. Patent and Trademark Office issued to the Company a patent claiming a sterile aqueous choline salt composition with a term expiring in 2041.
Second Quarter 2022 Financial Results

As of June 30, 2022, cash, cash equivalents and marketable debt securities were $112.8 million. The Company expects its current cash and cash equivalents will be sufficient to fund its planned operations into mid-2024.
Research and development (R&D) expenses for the second quarter of 2022 decreased to $3.1 million from $5.9 million during the second quarter of 2021. The decreased R&D expenses were primarily due to decreases in manufacturing expenses associated with TARA-002.
General and administrative expenses for the second quarter of 2022 decreased to $5.6 million from $6.9 million for the prior year period. The decrease was primarily due to decreases in stock-based compensation.
For the second quarter of 2022, Protara reported a net loss of $8.5 million, or $0.80 per share, compared with a net loss of $12.8 million, or $1.14 per share, for the same period in 2021. Net loss for the second quarter of 2022 included approximately $3.8 million of stock-based compensation expenses.
About TARA-002

TARA-002 is an investigational cell therapy in development for the treatment of NMIBC and LMs for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Picibanil in Japan and Taiwan by Chugai Pharmaceutical Co., Ltd. Protara has successfully demonstrated manufacturing comparability between TARA-002 and OK-432.

When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a strong immune cascade. Neutrophils, monocytes and lymphocytes infiltrate the abnormal cells and various cytokines, including interleukins IL-2, IL-6, IL-8, IL-10, IL-12, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor are secreted by immune cells to induce a strong local inflammatory reaction and destroy the abnormal cells.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

Bladder cancer is the 6th most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle.

About Lymphatic Malformations (LMs)

LMs are rare, congenital malformations of lymphatic vessels resulting in the failure of these structures to connect or drain into the venous system. Most LMs are present in the head and neck region and are diagnosed in early childhood during the period of active lymphatic growth, with more than 50% detected at birth and 90% diagnosed before the age of 3 years. The most common morbidities and serious manifestations of the disease include compression of the upper aerodigestive tract, including airway obstruction requiring intubation and possible tracheostomy dependence; intralesional bleeding; impingement on critical structures, including nerves, vessels, lymphatics; recurrent infection, and cosmetic and other functional disabilities.

About IV Choline Chloride and Intestinal Failure-associated Liver Disease (IFALD)

IV Choline Chloride is an investigational, intravenous (IV) phospholipid substrate replacement therapy initially in development for patients receiving parenteral nutrition (PN) who have IFALD. Choline is a known important substrate for phospholipids that are critical for healthy liver function. Because PN patients cannot sufficiently absorb adequate levels of choline and no available PN formulations contain sufficient amounts of choline to correct this deficiency, PN patients often experience a prolonged progression to hepatic failure and death, with the only known intervention being a dual small bowel/liver transplant. If approved, IV Choline Chloride would be the first approved therapy for IFALD. It has been granted Orphan Drug Designations (ODDs) by the FDA for the treatment of IFALD and the prevention of choline deficiency in PN patients.

On August 9, 2022 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported the publication of preclinical study results demonstrating the successful generation, durable anti-tumor response, and functional persistence of TCR-CAR+ iPSC-derived CD8αβ T cells from induced pluripotent stem cells (iPSCs) (Press release, Fate Therapeutics, AUG 9, 2022, View Source [SID1234617939]). The CD8αβ T cells were derived from a single engineered iPSC integrating a novel chimeric antigen receptor (CAR) transgene into the T-cell receptor alpha constant (TRAC) locus, ensuring complete bi-allelic disruption of T-cell receptor (TCR) expression and promoting uniform CAR expression. The discoveries were made under a multi-year research collaboration between the Company and Memorial Sloan Kettering Cancer Center (MSK) led by Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering and Head, Gene Expression and Gene Transfer Laboratory, and were published this week in Nature Biomedical Engineering.

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"Scientists have previously differentiated induced pluripotent stem cells to form CAR T cells, however, it was observed that premature αβTCR or constitutive CAR expression resulted in the derivation of innate-like T cells that do not acquire the phenotype nor exhibit the function of conventional CD8αβ T cells," said Dr. Sadelain. "Our published findings are the first to show the generation of iPSC-derived CD8αβ CAR T cells lacking a TCR, where timed and calibrated expression of the CAR in place of the TCR successfully drove T-cell maturation and promoted the acquisition of a transcriptional and functional profile more closely resembling that of natural CD8αβ T cells."

The mass production of TCR-CAR+ CD8αβ T cells from master engineered iPSC lines is a promising approach for development of off-the-shelf, cell-based cancer immunotherapies. Through a systematic assessment of factors that affect T-cell lineage commitment and induce adaptive T-cell formation, the researchers discovered that integrating the CAR construct into the TRAC locus delayed its expression and drove T-cell lineage commitment, and that regulation of CAR signaling strength promoted the generation of CD4+CD8+ double-positive cells mimicking thymic development in the absence of a TCR. Subsequent stimulation of the CAR matured the double-positive population into single-positive CD8αβ T cells with a phenotype highly correlated with peripheral blood CD8αβ effector T cells and distinct from γδ T cells and natural killer cells. Preclinical studies showed that iPSC-derived TCR-CAR+ CD8αβ T cells were able to repeatedly lyse tumor cells in vitro and durably control leukemia in vivo, with persistence in the bone marrow, spleen, and blood, in a systemic NALM6 leukemia model.

"These published findings continue to support our unique ability to generate TCR-CAR+ CD8αβ T cells from master engineered iPSC lines that exhibit a phenotypic profile and anti-tumor activity comparable to healthy donor-derived peripheral blood CAR T cells in preclinical model systems," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We believe our off-the-shelf, iPSC-derived CAR T cell programs overcome the numerous challenges associated with the manufacture, consistency, and reach of autologous and allogeneic CAR T cells, and we look forward to sharing initial clinical data from our landmark Phase 1 study of FT819 later this year."

The Company is conducting a multicenter Phase 1 study of FT819, the first T-cell therapy manufactured from a clonal master iPSC line to undergo clinical investigation. The product candidate’s clonal engineered master iPSC line is created from a single iPSC that has a novel CD19-targeted 1XX CAR construct integrated into the TRAC locus, ensuring complete bi-allelic disruption of TCR expression to prevent graft-versus-host disease and promoting uniform CAR expression for enhanced anti-tumor activity. Dose escalation is currently ongoing in single-dose and multi-dose escalation cohorts for relapsed / refractory B-cell malignancies.

Pursuant to a license agreement with MSK, Fate Therapeutics has an exclusive license for all human therapeutic use to U.S. Patent No. 10,370,452, which covers compositions and uses of effector T cells expressing a CAR, where such T cells are derived from a pluripotent stem cell including an iPSC. In addition to the patent rights licensed from MSK, the Company owns an extensive intellectual property portfolio that broadly covers compositions and methods for the genome editing of iPSCs using CRISPR and other nucleases, including the use of CRISPR to insert a CAR in the TRAC locus for endogenous transcriptional control.

Fate Therapeutics has licensed intellectual property from MSK on which Dr. Sadelain is an inventor. As a result of the licensing arrangement, MSK has financial interests related to Fate Therapeutics.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT819
FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease. FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia. FT819 is being investigated in a multicenter Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).

On August 9, 2022 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company focused on developing innovative and affordable oncology medicines to improve treatment outcomes and access for patients worldwide, reported that the global Phase 3 RATIONALE 301 trial with tislelizumab met its primary endpoint of non-inferior Overall Survival (OS) versus sorafenib as a first-line treatment in adult patients with unresectable hepatocellular carcinoma (HCC) (Press release, BeiGene, AUG 9, 2022, View Source [SID1234617938]). The safety profile for tislelizumab was consistent with previous studies and no new safety signals were reported. More than 600 patients in the U.S., Europe, and Asia participated in the study.

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HCC is the sixth most common type of cancer worldwide, accounting for more than 900,000 new cases in 2020i, and despite improvements in screening, surveillance rules, and imaging, more than two-thirds of patients with HCC present with advanced disease at diagnosisii.

"Patients with unresectable HCC face a devastating prognosis, with a median life expectancy of one year. Currently there are few treatment options if patients cannot tolerate TKI therapy or if their condition progresses," said Mark Lanasa M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. "We are encouraged by the outcome of the final analysis of RATIONALE 301 and look forward to sharing the full safety and efficacy results at an upcoming medical conference."

RATIONALE 301 (NCT03412773) is a global, Phase 3, randomized, open-label study of tislelizumab compared with sorafenib as a first-line treatment in adult patients with unresectable HCC. The primary endpoint of the study is non-inferiority of OS between the two treatment groups. The key secondary endpoint is Overall Response Rate, as assessed by Blinded Independent Review Committee (BIRC) per RECIST v1.1. Other secondary endpoints include other efficacy assessments such as Progression-Free Survival, Durability of Response, and Time to Progression per BIRC, as well as measures of health-related quality of life, and safety and tolerability.

About Tislelizumab

Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors. In pre-clinical studies, binding to Fcγ receptors on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.

Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.

The global tislelizumab clinical development program includes more than 11,000 subjects enrolled to-date in 30 countries and regions. BeiGene has initiated or completed 22 registration-enabling clinical trials. More information on the clinical trial program for tislelizumab can be found here.

BeiGene Oncology

BeiGene is committed to advancing best- and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D and medical affairs team of approximately 3,300 colleagues dedicated to advancing more than 100 clinical trials that have involved more than 16,000 subjects. Our expansive portfolio is directed predominantly by our internal colleagues supporting clinical trials in more than 45 countries and regions. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. BeiGene currently has three approved medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in the U.S., China, the European Union, Great Britain, Canada, Australia, and additional international markets; and the non-FC-gamma receptor binding anti-PD-1 antibody, tislelizumab, as well as the PARP inhibitor, pamiparib, in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen, Bristol Myers Squibb, EUSA Pharma and Bio-Thera. We also plan to address greater areas of unmet need globally through our other collaborations including with Mirati Therapeutics, Seagen, and Zymeworks.

In January 2021, BeiGene and Novartis announced a collaboration granting Novartis rights to co-develop, manufacture, and commercialize BeiGene’s anti-PD1 antibody, tislelizumab, in North America, Europe, and Japan. Building upon this productive collaboration, BeiGene and Novartis announced an option, collaboration, and license agreement in December 2021 for BeiGene’s TIGIT inhibitor, ociperlimab, that is in Phase 3 development. Novartis and BeiGene also entered into a strategic commercial agreement through which BeiGene will promote five approved Novartis Oncology products across designated regions of China.