On May 18, 2021 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, and City of Hope, a world-renowned independent cancer research and treatment center, reported that the first patient has been dosed in a clinical trial to establish the safety and feasibility of administering MB-101 (autologous IL13Rα2-CAR T cells) to patients with leptomeningeal brain tumors (e.g., glioblastoma, ependymoma or medulloblastoma) (Press release, Mustang Bio, MAY 18, 2021, View Source [SID1234580215]). The trial will enroll up to 30 patients and is taking place at City of Hope, where this chimeric antigen receptor T ("CAR T") cell therapy was initially developed. Even though it is a single center clinical trial, Mustang and City of Hope will facilitate patient transfers from other centers, as needed.

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All subjects enrolled in the Phase 1 single-center, two-arm clinical trial will undergo surgery for the placement of an intraventricular (ICV) Rickham catheter for CAR T cell delivery. The Phase 1 trial will determine the safety and feasibility of administering MB-101 through the ICV Rickham catheter over four weekly cycles in patients with glioblastoma (Arm 1) and ependymoma or medulloblastoma (Arm 2). The primary endpoints that will be evaluated are toxicity and survival at three months. Secondary endpoints include overall survival, CAR T and endogenous T cell levels, cytokine levels and phenotype detection in peripheral blood, tumor cyst fluid and cerebrospinal fluid.

Lisa Feldman, M.D., Ph.D., a neurosurgeon and assistant clinical professor in the Division of Neurosurgery at City of Hope and principal investigator of the clinical trial, commented, "Based on our research to date, including a previous clinical trial at City of Hope, further evaluation is warranted for this CAR T cell therapy. The prior clinical trial demonstrated encouraging potential of administering autologous IL13Rα2-CAR T cells intraventricularly to help treat patients with leptomeningeal brain tumors, a form of metastatic brain cancer that is difficult to treat. We continue to work closely with the Mustang team to potentially bring a safe, effective treatment option to patients suffering with this life-threatening disease."

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "The successful dosing of the first patient in this clinical trial of MB-101 is an important milestone in Mustang’s development program. We are pleased to support City of Hope to further study MB-101 in leptomeningeal brain tumors to potentially bring hope to patients suffering from this devastating and fatal disease. MB-101 has already demonstrated therapeutic potential when infused into the ventricular system, including delivering a complete response in a patient with leptomeningeal glioblastoma that was published in the New England Journal of Medicine. We aim to generate additional data that supports the advancement of this program."

Additional information about the trial can be found on clinicaltrials.gov using the identifier NCT04661384.

About MB‐101 (IL13Rα2‐specific CAR T cells)
IL13Rα2 is an attractive target for CAR T therapy as it has limited expression in normal tissue but is overexpressed on the surface of the majority of malignant glioma cells, including glioblastoma multiforme, ependymoma and medulloblastoma. CAR T cells are designed to express a membrane‐tethered IL‐13 receptor ligand (IL‐13) incorporating a single‐point mutation that provides high affinity for IL13Rα2 and reduces binding to IL13Rα1 in order to reduce healthy tissue targeting. Mustang is developing MB‐101 as an optimized CAR T product incorporating enhancements in CAR design and T cell engineering to improve antitumor potency and T cell persistence. MB‐101 includes a second‐generation hinge optimized CAR containing mutations in the IgG4 linker to reduce off‐target Fc interactions, the 4-1BB (CD137) co‐stimulatory signaling domain for improved persistence of CAR T cells and the extracellular domain of CD19 as a selection/safety marker. To further improve persistence, central memory T cells are enriched and genetically engineered using a manufacturing process that limits ex vivo expansion to reduce T cell exhaustion and maintain a memory T cell phenotype.

On May 18, 2021 Innovent Biologics, Inc. (HKEX: 01801) and Eli Lilly and Company (NYSE: LLY) reported that the U.S. Food and Drug Administration (FDA) accepted for review a Biologics License Application (BLA) for sintilimab injection in combination with pemetrexed and platinum chemotherapy for the first-line treatment of people with nonsquamous non-small cell lung cancer (NSCLC) (Press release, Innovent Biologics, MAY 18, 2021, View Source [SID1234580231]). This is the first U.S. regulatory submission of sintilimab, a PD-1 inhibitor being developed and commercialized under a global collaboration agreement between Innovent and Lilly.

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"The acceptance of this application – the first for sintilimab in the U.S. and outside of China – is an important milestone in Innovent’s global commercialization strategy and in our collaboration with Lilly," said Dr. Yongjun Liu, president of Innovent. "We look forward to working closely with the FDA to potentially bring this sintilimab-pemetrexed-platinum chemotherapy combination as a treatment option in the U.S., following the regimen’s regulatory approval in China earlier this year."

Sintilimab is currently being evaluated in a wide variety of cancer types under a broad clinical development program. To date, sintilimab has two indications approved in China, three regulatory submissions under review in China, and this regulatory application under review in U.S.. This regulatory application was submitted to the FDA in March 2021, primarily based on the results of the Phase 3 ORIENT-11 trial. The Prescription Drug User Fee Act (PDUFA) goal date for the FDA to make a decision on the sintilimab application is in March 2022. The FDA stated that it did not identify any potential review issues in its acceptance letter. It is currently planning to hold an Advisory Committee meeting to discuss this application.

"We are pleased the sintilimab submission is progressing. Our pursuit of this proposed indication in the U.S. reinforces Lilly’s and Innovent’s joint commitment to offer additional therapeutic options for people living with lung cancer and the healthcare providers who treat them," said Anne White, president, Lilly Oncology. "This is an encouraging start for our collaborative efforts to make sintilimab available in countries beyond China, as we continue to pursue opportunities globally for this immuno-oncology medicine across various tumor types."

About the ORIENT-11 Trial

ORIENT-11 is a randomized, double-blind, Phase 3 clinical trial assessing the efficacy and safety of sintilimab in combination with pemetrexed and platinum chemotherapy compared to placebo in combination with pemetrexed and platinum chemotherapy as a first-line treatment for patients with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC), with no sensitizing EGFR mutations or ALK rearrangements. The primary endpoint is progression-free survival (PFS) as assessed by Independent Radiographic Review Committee (IRRC) based on RECIST v1.1., and secondary endpoints include overall survival (OS) and safety profile.

A total of 397 patients were enrolled and randomized 2:1 to receive either sintilimab 200mg or placebo in combination with pemetrexed and platinum chemotherapy every three weeks for up to four cycles, followed by either sintilimab or placebo plus pemetrexed maintenance therapy. Patients received treatment until radiographic disease progression, unacceptable toxicity or any other conditions that required treatment discontinuation. Conditional crossover was permitted. The results of the ORIENT-11 study were published in 2020.1

About Lung Cancer

Globally, lung cancer is the leading cause of cancer death, killing nearly 1.8 million people worldwide each year. In the U.S., lung cancer is the second most common cancer (not counting skin cancer) and the leading cause of cancer death, responsible for nearly 25 percent of all cancer deaths – more than those from colorectal, breast and prostate cancers combined. Non-small cell lung cancer (NSCLC) accounts for approximately 85 percent of all lung cancers, and about 70 percent of those with NSCLC have the nonsquamous subtype. Fifty percent of NSCLC patients present with advanced or metastatic disease at diagnosis.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Lilly. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for:

The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of nonsquamous non-small cell lung cancer
Additionally, Innovent currently has regulatory submissions under review in China for sintilimab:

In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer
In combination with BYVASDA (bevacizumab injection) for the first-line treatment of hepatocellular carcinoma
The second-line treatment of squamous non-small cell lung cancer
In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non-small cell lung cancer.

Sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.

On May 18, 2021 Calliditas Therapeutics reported that Summary of Q1 2021 January 1 – March 31, 2021 (Press release, Calliditas Therapeutics, MAY 18, 2021, View Source [SID1234580180])

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No net sales for the three months ended March 31, 2021 were recognized. For the three months ended March 31, 2020 net sales amounted to SEK 0.5 million.
Operating loss amounted to SEK 150.8 million and SEK 72.3 million for the three months ended March 31, 2021 and 2020, respectively.
Loss before income tax amounted to SEK 136.2 million and SEK 63.7 million for the three months ended March 31, 2021 and 2020, respectively.
Loss per share before and after dilution amounted to SEK 2.51 and SEK 1.65, for the three months ended March 31, 2021 and 2020, respectively.
Cash amounted to SEK 867.3 million and SEK 728.6 million as of March 31, 2021 and 2020, respectively.
Significant events during Q1 2021, in summary
In January 2021, Calliditas announced a positive readout of the Phase 1 study with setanaxib, which enables clinical trials with higher dosing levels.
In January 2021, Calliditas shared the clinical development plan for setanaxib, including planned trials in Primary biliary cholangitis (PBC) and head and neck cancer, and additional data from Part A of NeflgArd study at its R&D Day.
In March 2021, Calliditas announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Nefecon in patients with primary IgA Nephropathy (IgAN).
Significant events after the end of reporting period, in summary
In April 2021, Calliditas was granted accelerated assessment procedure by the European Medicine Agency’s (EMA) Committee for Human Medicinal Products (CHMP) reducing the maximum timeframe for review of the application for marketing authorization. If approved, Nefecon could be available to patients in Europe in first half of 2022.
In April 2021, Calliditas announced that the FDA accepted the submission and granted Priority Review for the NDA for Nefecon. The FDA have set a Prescription Drug User Fee Act (PDUFA) goal date of September 15, 2021. Subject to approval, this would enable commercialization of Nefecon in the US in Q4, 2021.
Investor presentation May 18, 14:30 CET
Audio cast with teleconference, Q1 2021, May 18, 2021, 14:30 (Europe/Stockholm)

Webcast: View Source

Teleconference: SE: +46850558366 UK: + 443333009271 US: 18335268381

Financial calendar
Interim Report for the period January 1 – June 30, 2021 August 19, 2021

Interim Report for the period January 1 – September 30, 2021 November 18, 2021

Year-end Report for the period January 1 – December 31, 2021 February 24, 2022

On May 18, 2021 Iktos, a company specializing in Artificial Intelligence for new drug design, reported that it has entered into a Research Collaboration Agreement with Kadmon, a clinical-stage biopharmaceutical company based in New York, USA, pursuant to which, Iktos’s generative modelling artificial intelligence (AI) technology will be used to enable the rapid and cost-effective design of novel drug candidates for an undisclosed Kadmon drug discovery program (Press release, Kadmon, MAY 18, 2021, View Source [SID1234580216]). Under the agreement, Iktos will use its de novo structure-based generative modelling technology to identify novel compounds that match a pre-defined target product profile, with the aim of expediting Kadmon’s early phase discovery efforts.

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Kadmon discovers, develops and delivers small molecules and biologics to treat human diseases. Kadmon is expanding and integrating novel drug discovery platforms, with the aim of identifying and developing new product candidates for significant unmet medical needs. "Our collaboration with Iktos provides an exciting opportunity for Kadmon to combine Iktos’ innovative artificial intelligence (AI)-driven technology with Kadmon’s expertise in medicinal chemistry and structure-based drug design (SBDD) to accelerate novel target validation and to facilitate drug discovery", said Jean (Ji-In) Kim, Senior Vice President, Head of Chemistry at Kadmon.

Iktos’ AI technology, based on deep generative models, helps bring speed and efficiency to the drug discovery process. Iktos’ technology automatically designs virtual novel molecules that have all of the characteristics of a successful drug molecule. This approach, now validated through Iktos’ other collaborations, is a novel solution to one of the key challenges in drug design: rapid identification of molecules which simultaneously satisfy multiple critical drug criteria, such as potency, selectivity, safety, and project-specific properties. In early-stage discovery projects, Iktos’ technology allows the design of novel hits with optimal protein-ligand interactions, as predicted by molecular modelling technology. This approach enables the exploration of chemical space in a unique way and produces innovative molecule designs with greater Freedom to Operate. Furthermore, it drastically shortens the hit finding and hit-to-lead optimization phases by enabling multi-parametric in silico optimization from the start of a project.

"We are thrilled that Kadmon is engaging with Iktos to try expedite the discovery of a drug candidate on a promising target," commented Yann Gaston-Mathé, President and CEO of Iktos. "We are proud to have earned the trust of our collaborators and are confident that Iktos’ software will improve Kadmon’s medicinal chemists’ ability to identify promising novel chemical matter and solve complex multi parametric optimization problems. The feedback from Kadmon’s research team will be highly valuable as we work to improve our product offering. Our strategy has always been to tackle challenging problems alongside our collaborators where we can demonstrate value generation for new and on-going drug discovery projects."

On May 18, 2021 Epigenomics AG (Frankfurt Prime Standard: ECX, OTCQX: EPGNY, the "Company") reported that it has fully placed the new shares from the capital increase resolved on April 27, 2021 (Press release, Epigenomics, MAY 18, 2021, View Source [SID1234580181]). The offer was oversubscribed multiple times. Accordingly, the Company’s share capital will be increased from currently EUR 9,852,690.00 by EUR 1,970,537.00 to EUR 11,823,227.00 by 1,970,537 new registered shares of the Company against cash contributions.

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The gross proceeds from the capital increase amount to approximately EUR 2.2 million.

The capital increase needs to be registered in the commercial register, which the Executive Board will apply for shortly. The inclusion of the new shares under the Company’s existing listing (ISIN DE000A3H2184) of the remaining shares is currently expected to take place at or around May 26, 2021.