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Atara Biotherapeutics’ Ebvallo™ (tabelecleucel) Receives European Commission Approval as First Ever Therapy for Adults and Children with EBV+ PTLD

On December 19, 2022 Atara Biotherapeutics, Inc. (Nasdaq: ATRA) and Pierre Fabre reported that the European Commission (EC) has granted marketing authorization for Ebvallo (tabelecleucel) as a monotherapy for the treatment of adult and pediatric patients two years of age and older with relapsed or refractory Epstein‑Barr virus positive post‑transplant lymphoproliferative disease (EBV+ PTLD) who have received at least one prior therapy (Press release, Atara Biotherapeutics, DEC 19, 2022, View Source [SID1234625415]). For solid organ transplant patients, prior therapy includes chemotherapy unless chemotherapy is inappropriate.

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The approval follows a positive opinion in October by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) and is applicable to all 27 European Union member states plus Iceland, Norway, and Liechtenstein. The CHMP positive opinion is based on results from the pivotal Phase 3 ALLELE study.1 In this study, EbvalloTM demonstrated a favorable risk-benefit profile.

"The approval of EbvalloTM in Europe is a medical breakthrough for patients with significant unmet need," said Pascal Touchon, President and Chief Executive Officer of Atara. "As the first allogeneic, or donor-derived, T-cell immunotherapy to receive approval from any regulatory agency in the world, this marks a historic moment for Atara, our European partner, Pierre Fabre, and for the broader cell therapy field."

EBV+ PTLD is a rare, acute, and potentially deadly hematologic malignancy that occurs after transplantation when a patient’s T-cell immune response is compromised by immunosuppression. It can impact patients who have undergone solid organ transplant (SOT) or allogeneic hematopoietic cell transplant (HCT). Poor median survival of 0.7 months and 4.1 months for HCT and SOT, respectively, is reported in EBV+ PTLD patients for whom standard of care failed, underscoring the significant need for new therapeutic options.

Under a previously announced License Agreement with Atara, Pierre Fabre will lead all commercialization and distribution activities in Europe and select other markets, in addition to medical and regulatory activities following the transfer of the EbvalloTM Marketing Authorization Application (MAA) from Atara to Pierre Fabre.

"Ebvallo represents a significant moment in the cell therapy space and a breakthrough for European patients with EBV+ PTLD," said Eric Ducournau, CEO of Pierre Fabre, Atara’s commercialization partner in Europe. "We are proud and excited to bring this innovative therapy to the marketplace, which will reinforce Pierre Fabre’s portfolio in oncology, hematology, and rare diseases."

EbvalloTM has orphan designation in Europe. Orphan designation is reserved for medicines treating life-threatening or chronically debilitating diseases that are rare (affecting not more than five in 10,000 people in the EU). Authorized orphan medicines benefit from ten years of market exclusivity, protecting them from competition with similar medicines with the same therapeutic indication, which cannot be marketed during the exclusivity period.

UroGen Completes Enrollment of Its Phase 3 Clinical Trial for UGN-102 in Development for Low-Grade, Intermediate-Risk, Non-Muscle Invasive Bladder Cancer (LG-IR-NMIBC)

On December 19, 2022 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported that the Phase 3 ENVISION study of investigational agent UGN-102 (mitomycin) for intravesical solution in development for the treatment of LG-IR-NMIBC is fully enrolled. The ENVISION study targeted enrollment of 220 patients across 90 sites and, assuming positive findings, UroGen anticipates submitting a New Drug Application (NDA) for UGN-102 in 2024 (Press release, UroGen Pharma, DEC 19, 2022, View Source [SID1234625414]).

"Completing enrollment for the ENVISION trial is a major milestone that brings us one step closer to validating chemoablation for the treatment of LG-IR-NMIBC," said Sandip Prasad, M.D., M.Phil., Director of Genitourinary Surgical Oncology, Morristown Medical Center, Atlantic Health System, NJ, and lead study investigator for the ENVISION trial. "These patients are burdened with disease recurrences and repeat surgeries that take a toll on an elderly population who often have co-morbidities that increase the risks associated with surgery. If successful ENVISION has the potential to fundamentally change the way we treat these patients."

ENVISION is a Phase 3, single-arm, multinational, multicenter study evaluating the efficacy and safety of UGN-102 as primary chemoablative therapy, in 220 patients with LG-IR-NMIBC from 90 sites. The design for the Phase 3 ENVISION trial is similar to the Phase 2b OPTIMA II trial in that the patient population will have similar clinical characteristics, receive the same treatment regimen and undergo the same efficacy and safety assessments and qualitative follow-up. Patients enrolled in ENVISION will receive six once-weekly intravesical instillations of UGN-102. The primary endpoint is the complete response rate at PDE (primary disease evaluation) which will typically occur within three months from the first instillation, and the key secondary endpoint will be durability of response in patients who achieve complete response.

"We are optimistic about the clinical potential of UGN-102 because ENVISION shares a similar approach to the successful OPTIMA II Phase 2b study," said Mark Schoenberg, Chief Medical Officer, UroGen. "Also, our chemoablative treatment for low-grade upper tract urothelial cancer and UGN-102 uses our proprietary RTGel technology, and the urothelial lining in the bladder and upper tract is similar. If approved UGN-102 may offer additional advantages because it is instilled into the bladder via urethral catheter in an outpatient setting – a common procedure in most urologists’ offices."

If approved UGN-102 has the potential to offer a simpler, minimally invasive, and non-surgical option to transurethral resection of bladder tumor (TURBT), as UGN-102 can be administered without the use of anesthesia or special equipment. UroGen’s first product and UGN-102 utilize mitomycin as their active pharmaceutical ingredient, although in a different ratio and both allow for local delivery and sustained exposure to mitomycin for up to six hours.

About LG-IR-NMIBC

Approximately 800,000 people are living with bladder cancer in the U.S., of that 80,000 suffer from LG-IR-NMIBC. Patients with LG-IR-NMIBC face a future of recurrence and additional surgeries. Currently, the only primary treatment available is a surgical procedure known as TURBT, which requires anesthesia. Every time TURBT is performed it may impose more burden and serious risks on patients, including pain, bleeding, infection and injury (including perforation).

About UGN-102

UGN-102 (mitomycin) for intravesical solution is an investigational drug formulation of mitomycin in Phase 3 development for the treatment of LG-IR-NMIBC. Utilizing UroGen’s proprietary RTGel technology, a sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter in an outpatient setting. Assuming positive findings from the ENVISION Phase 3 study, UroGen anticipates submitting a New Drug Application (NDA) for UGN-102 in 2024. If approved, UGN-102 would be the first non-surgical primary therapeutic to treat a subset of bladder cancer characterized by high recurrence rates and multiple surgeries.

Revolution Medicines Announces Publication Describing Design and Synthesis of RMC-5552, a First-in-Class, Bi-Steric mTORC1-Selective Inhibitor

On December 19, 2022 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for RAS-addicted cancers, reported publication of a manuscript in the Journal of Medicinal Chemistry that details the discovery efforts leading to RMC-5552, the company’s first-in-class, bi-steric mTORC1-selective inhibitor (Press release, Revolution Medicines, DEC 19, 2022, View Source [SID1234625413]). The manuscript describes the unprecedented compound profile that includes 40-fold selectivity for mTORC1 over mTORC2 and greater than 53-fold selectivity over other lipid kinases. The paper also shows that selective mTORC1 inhibition using the company’s related preclinical tool compound (RMC-6272) in combination with a covalent KRASG12C inhibitor induced tumor regressions in a preclinical model of KRASG12C mutant non-small cell lung cancer (NSCLC) that exhibits resistance to KRASG12C inhibitor monotherapy.

RMC-5552 is designed to suppress phosphorylation and inactivation of 4EBP1, a key translational regulator of oncogene expression, in cancers with hyperactive mTORC1 signaling. This bi-steric compound is designed to bind simultaneously to two different sites on mTORC1 to drive deep inhibition of mTORC1 while maintaining selectivity for mTORC1 over mTORC2, a unique profile compared to prior generations of mTOR inhibitors. Revolution Medicines is currently evaluating RMC-5552 as monotherapy in a Phase 1/1b clinical trial in patients with refractory solid tumors (NCT04774952), and initial antitumor activity has been reported. The company plans to evaluate RMC-5552 in combination with RAS(ON) inhibitors in patients with cancers harboring mutations in both RAS and the mTOR pathways.

"The Journal of Medicinal Chemistry manuscript details the sophisticated structure-based chemical design and synthesis employed by our drug discovery team that produced RMC-5552," said Steve Kelsey, M.D., president, research and development at Revolution Medicines. "The differentiated antitumor and tolerability profile of RMC-5552 in the preclinical setting compared to earlier mTORC inhibitors provides a strong rationale for evaluating it in patients with tumors that have abnormally high mTORC1 growth signaling, including in combination with our RAS(ON) Inhibitors in patients with tumors that have both RAS and mTORC1 pathway co-mutations."

The manuscript published in the Journal of Medicinal Chemistry is titled, "Discovery of RMC-5552, a Selective Bi-Steric Inhibitor of mTORC1, for the Treatment of mTORC1-activated Tumors," and can be accessed at: View Source

About mTORC1

The mTOR Complex 1 (mTORC1) is a central node within the mTOR signaling pathway and a critical regulator of metabolism, growth, and proliferation in cancer cells. Oncogenic mutations of genes encoding proteins that lie upstream of mTOR, including PI3K, PTEN, and STK11, can drive abnormal activation of mTORC1 and subsequent inactivation of the tumor suppressor 4EBP1. Selective inhibition of mTORC1 to reactivate 4EBP1 is a potential therapeutic strategy for patients with tumors bearing such mutations. These mutations are often co-occurring with RAS mutations in RAS-addicted tumors and combinations of mTORC1- and RAS-targeted inhibitors may be of particular benefit in this context.

Regeneron Announces Presentation at the 41st Annual J.P. Morgan Healthcare Conference

On December 19, 2022 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that it will webcast its presentation at the 41st Annual J.P. Morgan Healthcare Conference on Monday, January 9, 2023 (Press release, Regeneron, DEC 19, 2022, View Source [SID1234625412]). The presentation is scheduled for 9:00 a.m. Pacific Time (12:00 p.m. Eastern Time) and may be accessed from the "Investors & Media" page of Regeneron’s website at View Source An archived version of the presentation will be available for at least 30 days.

Perrigo to Host Virtual Investor Day on February 28, 2023

On December 19, 2022 Perrigo Company plc (NYSE: PRGO), a leading global provider of Consumer Self-Care Products, reported that it will host a Virtual Investor Day on February 28, 2023, in conjunction with its regular quarterly earnings (Press release, Perrigo Company, DEC 19, 2022, View Source,-2023 [SID1234625411]). At that meeting, management will share the Company’s 2023-2025 strategic plans to Optimize and Accelerate the performance of the recently transformed Company through a continuation of strong net sales and market share growth, a global supply chain initiative designed to substantively increase gross margins, a focus on cash generation and a capital allocation plan that prioritizes dividends and debt reduction. The event will begin at 8:00 a.m. EST and feature presentations from executive leadership.

A live audio webcast of the Investor Day, including the Q&A session, and the accompanying presentation will be available at View Source A replay will also be available.