On June 30, 2021 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported the U.S. Food and Drug Administration (FDA) approval of Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) for use as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) in pediatric and adult patients one month and older who have developed hypersensitivity to E. coli-derived asparaginase (Press release, Jazz Pharmaceuticals, JUN 30, 2021, View Source [SID1234584521]).1 Rylaze is the only recombinant erwinia asparaginase manufactured product that maintains a clinically meaningful level of asparaginase activity throughout the entire duration of treatment, and it was developed by Jazz to address the needs of patients and healthcare providers with an innovative, high-quality erwinia-derived asparaginase with reliable supply.

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"We are excited to bring this important new treatment to patients who are in critical need, and we are grateful to FDA for the approval of Rylaze based on its established safety and efficacy profile. We are pleased Rylaze was approved before the trial is complete and are diligently working to advance additional clinical trial data. We are committed to quickly engaging with FDA to evolve the Rylaze product profile with additional dosing options and an IV route of administration," said Bruce Cozadd, chairman and CEO of Jazz Pharmaceuticals. "Thank you to our collaborators within the Children’s Oncology Group, the clinical trial investigators, patients and their families, and all of the other stakeholders who helped us achieve this significant milestone."

Rylaze was granted orphan drug designation for the treatment of ALL/LBL by FDA in June 2021. The Biologics Licensing Application (BLA) approval followed review under the Real-Time Oncology Review (RTOR) program, an initiative of FDA’s Oncology Center of Excellence designed for efficient delivery of safe and effective cancer treatments to patients.

The company expects Rylaze will be commercially available in mid-July.

"The accelerated development and approval of Rylaze marks an important step in bringing a meaningful new treatment option for many ALL patients – most of whom are children – who cannot tolerate E. coli-derived asparaginase medicine," said Dr. Luke Maese, assistant professor at the University of Utah, Primary Children’s Hospital and Huntsman Cancer Institute. "Before the approval of Rylaze, there was a significant need for an effective asparaginase medicine that would allow patients to start and complete their prescribed treatment program with confidence in supply."

Recent data from a Children’s Oncology Group retrospective analysis of over 8,000 patients found that patients who did not receive a full course of asparaginase treatment due to associated toxicity had significantly lower survival outcomes – regardless of whether those patients were high risk or standard risk, slow early responders.2

About Study JZP458-201
The FDA approval of Rylaze, also known as JZP458, is based on clinical data from an ongoing pivotal Phase 2/3 single-arm, open-label, multicenter, dose confirmation study evaluating pediatric and adult patients with ALL or LBL who have had an allergic reaction to E. coli-derived asparaginases and have not previously received asparaginase erwinia chrysanthemi. The study was designed to assess the safety, tolerability and efficacy of JZP458. The determination of efficacy was measured by serum asparaginase activity (SAA) levels. The Phase 2/3 study is being conducted in two parts. The first part is investigating the intramuscular (IM) route of administration, including a Monday-Wednesday-Friday dosing schedule. The second part remains active to further confirm the dose and schedule for the intravenous (IV) route of administration.

The FDA approval of Rylaze was based on data from the first of three IM cohorts, which demonstrated the achievement and maintenance of nadir serum asparaginase activity (NSAA) greater than or equal to the level of 0.1 U/mL at 48 hours using IM doses of Rylaze 25 mg/m2. The results of modeling and simulations showed that for a dosage of 25 mg/m2 administered intramuscularly every 48 hours, the proportion of patients maintaining NSAA ≥ 0.1 U/mL at 48 hours after a dose of Rylaze was 93.6% (95% CI: 92.6%, 94.6%).1

The most common adverse reactions (incidence >15%) were abnormal liver test, nausea, musculoskeletal pain, fatigue, infection, headache, pyrexia, drug hypersensitivity, febrile neutropenia, decreased appetite, stomatitis, bleeding and hyperglycemia. In patients treated with the Rylaze, a fatal adverse reaction (infection) occurred in one patient and serious adverse reactions occurred in 55% of patients. The most frequent serious adverse reactions (in ≥5% of patients) were febrile neutropenia, dehydration, pyrexia, stomatitis, diarrhea, drug hypersensitivity, infection, nausea and viral infection. Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received Rylaze. Adverse reactions resulting in permanent discontinuation included hypersensitivity (6%) and infection (3%).1

The company will continue to work with FDA and plans to submit additional data from a completed cohort of patients evaluating 25mg/m2 IM given on Monday and Wednesday, and 50 mg/m2 given on Friday in support of a M/W/F dosing schedule. Part 2 of the study is evaluating IV administration and is ongoing. The company also plans to submit these data for presentation at a future medical meeting.

Investor Webcast
The company will host an investor webcast on the Rylaze approval in July. Details will be announced separately.

About Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn)
Rylaze, also known as JZP458, is approved in the U.S. for use as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) in pediatric and adult patients one month and older who have developed hypersensitivity to E. coli-derived asparaginase. Rylaze has orphan drug designation for the treatment of ALL/LBL in the United States. Rylaze is a recombinant erwinia asparaginase that uses a novel Pseudomonas fluorescens expression platform. JZP458 was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) in October 2019 for the treatment of this patient population. Rylaze was approved as part of the Real-Time Oncology Review program, an initiative of the FDA’s Oncology Center of Excellence designed for efficient delivery of safe and effective cancer treatments to patients.

The full U.S. Prescribing Information for Rylaze is available at: <View Source>

Important Safety Information

RYLAZE should not be given to people who have had:

Serious allergic reactions to RYLAZE
Serious swelling of the pancreas (stomach pain), serious blood clots, or serious bleeding during previous asparaginase treatment
RYLAZE may cause serious side effects, including:

Allergic reactions (a feeling of tightness in your throat, unusual swelling/redness in your throat and/or tongue, or trouble breathing), some of which may be life-threatening
Swelling of the pancreas (stomach pain)
Blood clots (may have a headache or pain in leg, arm, or chest)
Bleeding
Liver problems
Contact your doctor immediately if any of these side effects occur.

Some of the most common side effects with RYLAZE include: liver problems, nausea, bone and muscle pain, tiredness, infection, headache, fever, allergic reactions, fever with low white blood cell count, decreased appetite, mouth swelling (sometimes with sores), bleeding, and too much sugar in the blood.

RYLAZE can harm your unborn baby. Inform your doctor if you are pregnant, planning to become pregnant, or nursing. Females of reproductive potential should use effective contraception (other than oral contraceptives) during treatment and for 3 months following the final dose. Do not breastfeed while receiving RYLAZE and for 1 week after the final dose.

Tell your healthcare provider if there are any side effects that are bothersome or that do not go away.

These are not all the possible side effects of RYLAZE. For more information, ask your healthcare provider.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088 (1-800-332-1088).

About ALL
ALL is a cancer of the blood and bone marrow that can progress quickly if not treated.3 Leukemia is the most common cancer in children, and about three out of four of these cases are ALL.4 Although it is one of the most common cancers in children, ALL is among the most curable of the pediatric malignancies due to recent advancements in treatment.5,6 Adults can also develop ALL, and about four of every 10 cases of ALL diagnosed are in adults.7 The American Cancer Society estimates that almost 6,000 new cases of ALL will be diagnosed in the United States in 2021.7 Asparaginase is a core component of multi-agent chemotherapeutic regimens in ALL.8 However, asparaginase treatments derived from E. coli are associated with the potential for development of hypersensitivity reactions.9

About Lymphoblastic Lymphoma
LBL is a rare, fast-growing, aggressive subtype of Non-Hodgkin’s lymphoma, most often seen in teenagers and young adults.8 LBL is a very aggressive lymphoma – also called high-grade lymphoma – which means the lymphoma grows quickly with early spread to different parts of the body.10,11

On June 30, 2021 Dr. Reddy’s Laboratories Limited (BSE: 500124, NSE: DRREDDY, NYSE: RDY, NSEIFSC: DRREDDY, along with its subsidiaries together referred to as "Dr. Reddy’s") reported that its Annual Report on Form 20-F containing its consolidated financial statements for the fiscal year ended March 31, 2021 and prepared in accordance with the International Financial Reporting Standards (IFRS) as issued by the International Accounting Standards Board was filed with the United States Securities and Exchange Commission (SEC) on June 30, 2021 (Press release, Dr Reddy’s, JUN 30, 2021, View Source [SID1234584520]).

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The Annual Report on Form 20-F is also available on the website of Dr. Reddy’s, www.drreddys.com. American Depositary Receipts (ADRs) holders may also obtain a hard copy of the Annual Report on Form 20-F at no cost, by sending a written request to the Company’s registered office or by sending an e-mail to [email protected].

On June 30, 2021 NANOBIOTIX (Euronext : NANO –– NASDAQ: NBTX – the ‘‘Company’’), a late-clinical stage biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, reported the initiation of a new phase I study evaluating NBTXR3 activated by radiation therapy (RT) for patients with non-small cell lung cancer (NSCLC) amenable to re-irradiation (Press release, Nanobiotix, JUN 30, 2021, View Source [SID1234584519]). The phase I is among five collaborator-led studies that are active and recruiting at The University of Texas MD Anderson Cancer Center (MD Anderson), and the third to enroll its first patient.

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"Our ongoing collaboration with MD Anderson remains a critical component of our strategy as we seek to develop NBTXR3 as a solid tumor-agnostic, therapeutic combination-agnostic agent with the potential to change the practice of radiotherapy and immunotherapy," said Laurent Levy, co-founder and chief executive officer of Nanobiotix. "These collaborator-led studies not only provide patients with significant unmet need the opportunity to benefit from MD Anderson’s physicians, but also provide additional capacity for Nanobiotix to expand development of NBTXR3 into indications where innovation is urgently needed while remaining focused internally on our priority pathways in head and neck cancer and immunotherapy."

A Phase I Study of Reirradiation with NBTXR3 for Inoperable Locoregional Recurrent Non-Small Cell Lung Cancer

This phase I study, led by Saumil Gandhi, Assistant Professor, Department of Radiation Oncology, Division of Radiation Oncology, MD Anderson, investigates the safety and optimal dose of NBTXR3 when activated by radiation therapy for the treatment of non-small cell lung cancer that cannot be treated by surgery (inoperable) and has come back (recurrent). The study has a two-cohort, open label design consisting of two parts: (i) RT safety lead-in cohort recruiting up to 10 patients and NBTXR3 activated by RT dose-finding cohort recruiting up to 12 patients; and (ii) expansion at the recommended phase II dose (RP2D) with toxicity monitoring recruiting 12 patients. The dose levels explored to be explored are 22% and 33% of baseline gross tumor volume. The planned enrollment period is up to three years.

The patient population includes adults (age ≥ 18 years) with medically inoperable NSCLC with overlap between recurrent disease in need of treatment and prior RT. Given the design of the study, patients in the first cohort in part one will receive RT and be monitored for safety before the second cohort is opened where patients will receive injections of NBTXR3.

Five Studies Now Active and Recruiting in Clinical Collaboration

In addition to the lung cancer study described above, two phase II studies, each evaluating NBTXR3 in combination with anti-PD-1 for patients with head and neck cancer (inoperable locoregional recurrent amenable to reirradiation and recurrent metastatic with limited PD-L1 expression or refractory); one phase I study evaluating NBTXR3 in combination with chemotherapy for patients with esophageal cancer; and one phase I study evaluating NBTXR3 as a single-agent activated by RT for patients with pancreatic cancer are active and enrolling. As previously announced, the first patient has been injected with NBTXR3 in each of the esophageal cancer and pancreatic cancer studies. The first NBTXR3 injections in the phase II head and neck cancer studies are expected in the second half of 2021. All studies in the collaboration are led by MD Anderson and milestones will be reported as they are made available by the institution.

Next Steps for Collaborator-led Expansion of NBTXR3 Development as a Potentially Solid Tumor-Agnostic and Therapeutic Combination-Agnostic Agent

The clinical collaboration between Nanobiotix and MD Anderson is a collaborator-led expansion of the NBTXR3 development pipeline across indications and therapeutic combinations. One additional study evaluating NBTXR3 in combination with anti-CTLA-4 and anti-PD-1/L1 plus RadScopal in advanced solid tumors with lung or liver metastasis is planned to launch in the second half of 2021. Further studies evaluating the potential of NBTXR3 to address unmet needs throughout the oncology landscape are in discussion as part of the collaboration agreement and updates will be provided as the planning process evolves.

About NBTXR3

NBTXR3 is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. The product candidate’s physical mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the physical MoA, Nanobiotix believes that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.

NBTXR3 is being evaluated in locally advanced head and neck squamous cell carcinoma (HNSCC) as the primary development pathway. The Company-sponsored phase I dose escalation and dose expansion study has produced favorable safety data and early signs of efficacy; and a phase III global registrational study is planned to launch in the second half of 2021. In February 2020, the United States Food and Drug Administration granted regulatory Fast Track designation for the investigation of NBTXR3 activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy—the same population being evaluated in the planned phase III study.

Nanobiotix has also prioritized an Immuno-Oncology development program—beginning with a Company-sponsored phase I clinical study evaluating NBTXR3 activated by radiotherapy in combination with anti-PD-1 checkpoint inhibitors for patients with locoregional recurrent or recurrent/metastatic HNSCC and lung or liver metastases from any primary cancer eligible for anti-PD-1 therapy.

Given the Company’s focus areas, and balanced against the scalable potential of NBTXR3, Nanobiotix has engaged in a strategic collaboration strategy with world class partners to expand development of the product candidate in parallel with its priority development pathways. Pursuant to this strategy, in 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several phase I and phase II studies to evaluate NBTXR3 across tumor types and therapeutic combinations.

On June 30, 2021 McKesson Corporation (NYSE: MCK) reported that it will release its first quarter fiscal 2022 financial results after market close on Wednesday, August 4, 2021 (Press release, McKesson, JUN 30, 2021, View Source [SID1234584518]). The company will host a live webcast of the earnings conference call for investors at 4:30 PM Eastern Time to review its financial results.

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The live webcast will be available on McKesson’s Investor Relations website at View Source, along with the company’s earnings press release, financial tables and slide presentation.

On June 30, 2021 Medsenic, a clinical-stage biopharmaceutical company focused on the discovery and development of novel indications and formulations of arsenic salts for the treatment of severe autoimmune diseases, reported that it has entered into an exclusive licensing agreement with Australian company Phebra for the development of their patented OATO formulation (Oral Arsenic Trioxide) in the treatment of autoimmune diseases (Press release, Phebra, JUN 30, 2021, View Source [SID1234584517]).

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This agreement is a major step in paving the way for the marketing of a second generation of Medsenic’s drug candidates, until now dispensed as an intravenous solution (Arscimed). Phebra’s expertise in drug development, together with Medsenic’s clinically validated scientific discoveries, will confirm further the efficacy of arsenic trioxide observed in a phase 2 study, by switching to the novel and patient administered oral form (OATO).

"We are delighted with this partnership with Phebra, a global reference player renowned for its unique expertise in the development and formulation of critical care medicines and a specific expertise in arsenic-based drugs. This exclusive agreement reflects Medsenic’s commitment to pursue the development of its pipeline of drug candidates targeting autoimmune diseases ; it will allow us to initiate our Phase 3 clinical trial for the treatment of cGvHD and to develop our products in new indications such as systemic sclerosis", said Prof. François Rieger, President and co-founder of Medsenic, who added: "The robust formulation of Arscimed is a real paradigm shift in that it will bring expected comfort to patients with chronic graft-versus-host disease."

"We are impressed by the clinical results obtained by Medsenic with its product Arscimed in the treatment of cGvHD as an intravenous solution. We are confident that the properties of arsenic trioxide observed in various clinical studies have the potential to revolutionize the therapeutic management of autoimmune diseases where there remains a huge unmet medical need. With our novel patented oral formulation, we will contribute to a significant improvement in patient care, avoiding frequent hospital stays, painful injections and potentially less adverse side effects," said Dr Mal Eutick, President of Phebra.

About the ATO :

Arsenic trioxide has the dual property of increasing cellular oxidative stress, to the point where it induces the programmed death of activated cells (enhanced apoptosis) and of modulating their production of proinflammatory cytokines. It thus has a specific long-term immunomodulatory effect on activated cells of the innate immune system, without affecting its normal components, as demonstrated in animal models without autoimmune pathology, and with perfectly controlled side effects. It probably acts at an upstream coordination level of the immune cascade, since a correction of all parameters signaling the autoimmune cascade is observed in various animal models of autoimmunity.

Research programs are being developed to understand the positive effects of arsenic trioxide in human clinical trials. MEDSENIC has provided initial proof of concept in a Phase 2a clinical trial for the treatment of severe systemic lupus erythematosus, followed by positive results in the treatment of cGvHD in Phase 2 (75% success rate in the full analysed population). Medsenic has demonstrated that its arsenic trioxide-based treatment has minimal toxicity and proven efficacy, leading to its wider application in other autoimmune diseases.