On September 17, 2018 Cytori Therapeutics (NASDAQ: CYTX) ("Cytori" or the "Company") reported that it received FDA orphan drug designation for its ATI-1123 chemotherapy drug product candidate, an albumin-stabilized pegylated liposomal docetaxel, for the treatment of small cell lung cancer (Press release, Cytori Therapeutics, SEP 17, 2018, View Source [SID1234529464]).

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The FDA’s Orphan Drug Designation Program provides orphan status to drugs, such as ATI-1123, which are intended for the safe and effective treatment of rare diseases/disorders that affect fewer than 200,000 people in the U.S. Sponsors of a drug receiving orphan designation qualify for various incentives including tax credits for clinical testing, 7 years of marketing exclusivity following FDA approval, and a waiver of prescription drug user fees.

Small cell lung cancer (SCLC), which accounts for approximately 15% of bronchogenic carcinomas with 33,375 new cases and 23,380 deaths estimated for 2017, has been identified by Cytori as a compelling target for ATI-1123. While SCLC is responsive to chemotherapy and radiation therapy, cure occurs only in ~20% of patients, generally restricted to those with limited stage disease. The remaining 80% of patients, including all patients with extensive disease, relapse within months of completing their initial therapy. Availability of 2nd line therapy options are limited, toxic, and provide little benefit in terms of extending survival. Topotecan is the only FDA-approved agent for 2nd line treatment of SCLC and is associated with an overall response rate of 24%, median response duration or time to progression of 14 weeks, and median overall survival of 25 weeks. Treatment usually involves a consecutive 5 day regimen of either IV or oral administration of drug, both which have black box warnings for severe myelosuppression as their use is associated with substantial morbidity including bone marrow suppression leading to neutropenia, thrombocytopenia and anemia requiring interventions of transfusion and growth factor support.

No major treatment advances for SCLC have occurred over the past 30 years. Hence, there remains a significant unmet need for novel agents with better safety profiles both for patients who cannot tolerate the adverse effects of 1st line chemo-radiotherapy and for relapsed/refractory patients who receive Topotecan. Cytori’s ATI-1123 has been designed to fill this need. ATI-1123’s combination of improved liposome stability, reduced toxicity, and superior delivery are expected to provide a therapeutic for SCLC that offers comparable or better efficacy to currently-available standards while having a less intensive administration routine and improved side effect profile.

Cytori is also exploring the development of ATI-1123 to address the shortcomings of docetaxel, a workhorse chemotherapy drug which generated $2.7B in worldwide sales at its peak. Compared to docetaxel, ATI-1123 may have potential to improve safety by removing the need for unwanted solvents, reduce morbidity by eliminating the requirement for standard pretreatment medications, provide better patient convenience and comfort via less time spent in the treatment center, decrease the cost of therapy, and enhance systemic docetaxel exposure.

A U.S. Phase 1 clinical study of ATI-1123 has been completed and published. Of the 29 patients in the study with cervical, gastric, melanoma, non-small cell lung, ovarian, pancreatic, prostate, thyroid, urachal and uterine cancers, 82% demonstrated a clinical benefit with ATI-1123. ATI-1123 exhibited an improved safety profile versus the Taxotere label with a 31% reduction in neutropenia and anemia. Further, ATI-1123 showed a 20% increase in maximum tolerated dose versus standard docetaxel and signs of efficacy with 1 partial responder.

On September 16, 2018 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported four oral clinical data presentations on two of its late-stage investigational therapies, tislelizumab and zanubrutinib, at the 21st Annual Meeting of the Chinese Society of Clinical Oncology (CSCO) (Press release, BeiGene, SEP 16, 2018, View Source [SID1234529451]). The meeting will take place September 19 – 23 in Xiamen, China. Tislelizumab is an investigational anti-PD-1 antibody, and zanubrutinib is an investigational small molecule inhibitor of Bruton’s tyrosine kinase (BTK).

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Oral Presentations:

Title: Clinical Profile of Tislelizumab in Chinese Patients with Microsatellite Instability High (MSI-H) or Mismatch Repair-Deficient (MMRd) Solid Tumors: Preliminary Results from an Indication-Expansion Cohort
Abstract ID: 449
Location: Second Floor, Straits Hall
Date: Thursday, September 20, 2018
Time: 16:45 – 16:55 (CST)
Presenter: Lin Shen, M.D.


Title: Tislelizumab Combined with Chemotherapy as First-Line Treatment in Chinese Patients (Pts) with Advanced Lung Cancer
Abstract ID: 450
Location: First Floor, Concert Hall
Date: Friday, September 21, 2018
Time: 11:30 – 11:38 (CST)
Presenter: Jie Wang, M.D., Ph.D.


Title: Preliminary Results with Tislelizumab in Chinese Patients with Non-Small Cell Lung Cancer (NSCLC)
Abstract ID: 448
Location: First Floor, Concert Hall
Date: Friday, September 21, 2018
Time: 11:38 – 11:45 (CST)
Presenter: Qing Zhou, M.D.


Title: A Phase 1 Clinical Study to Investigate the Safety, Tolerability and Pharmacokinetics/Pharmacodynamics of BTK Inhibitor BGB-3111 in Chinese Patients with B-Cell Lymphoma
Abstract ID: N/A
Location: First Floor, G Hall
Date: Saturday, September 22, 2018
Time: 08:30 – 08:45 (CST)
Presenter: Jun Zhu, M.D.

About Tislelizumab
Tislelizumab (BGB-A317) is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. Discovered by BeiGene scientists in Beijing, tislelizumab is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. Tislelizumab has demonstrated high affinity and specificity for PD-1. It is potentially differentiated from the currently approved PD-1 antibodies in an engineered Fc region, which is believed to minimize potentially negative interactions with other immune cells, based on preclinical data. Tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. BeiGene and Celgene Corporation have a global strategic collaboration for the development of tislelizumab in solid tumor cancers outside of Asia (except Japan). Tislelizumab’s new drug submission for the treatment of patients with relapsed/refractory classical Hodgkin’s lymphoma (R/R cHL) has been accepted and is under review by the National Medical Products Administration of China (NMPA, formerly known as CFDA or CDA).

About Zanubrutinib
Zanubrutinib (BGB-3111) is an investigational small molecule inhibitor of Bruton’s tyrosine kinase (BTK) that was discovered in BeiGene’s research facilities in Beijing, China. It is currently being evaluated in a broad pivotal clinical program globally and in China as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Zanubrutinib is under review as a Category 1 new drug submission for the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL) by the NMPA of China.

On September 14, 2018 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH), reported its consolidated financial results for the first six months of 2018 (Press release, Innate Pharma, SEP 14, 2018, View Source [SID1234529426]). The financial statements are attached to this press release.

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"In the first half of 2018 we have continued to advance our innovative portfolio, both with our partnered and proprietary immuno-oncology programs. We are encouraged by the emerging clinical data from our lead antibody, monalizumab, and look forward to presenting the updated data set from the Phase I/II study of monalizumab in combination with cetuximab in patients with recurrent or metastatic head and neck cancer at the upcoming ESMO (Free ESMO Whitepaper) 2018 congress," commented Mondher Mahjoubi, Chief Executive Officer of Innate Pharma. "Our commitment to continue the clinical development momentum remains a priority. Together with our partner AstraZeneca/MedImmune, we recently decided to recruit additional patients into the monalizumab plus cetuximab study to gain more experience in patients with advanced SCCHN** previously treated with anti-PD-1/L1. The Phase I trial evaluating IPH5401 in combination with durvalumab has been initiated and we look forward to share new data on IPH4102."

A conference call will be held today at 2:00pm (CEST)

Dial in numbers:

France and International: +33 (0)1 72 72 74 03 US only: +1 646 722 4916

PIN code: 53841185#

The presentation is available at the bottom of this page.

A replay is available on Innate Pharma’s website.

Financial highlights of the first half of 2018

The key elements of Innate Pharma’s financial results for the first half of 2018 are as follows:

Cash, cash equivalents and financial assets (current and non-current) amounting to €141.6m (million euros) as of June 30, 2018 (€176.6m as of December 31, 2017).
Financial liabilities amounting to €5.2m, including €3.9m of non-current liabilities (€5.9m as of December 31, 2017, including €4.5m of non-current liabilities).
Revenue and other income amounting to €23.7m (€21.2m for the first half of 2017). This amount mainly results from revenue from licensing and collaboration agreements (€16.9m) and from research tax credit (€6.2m).
Revenue related to the licensing and collaboration agreements mainly results from phasing of initial payment received by Innate Pharma in the context of the agreement signed in April 2015 relating to monalizumab with AstraZeneca/MedImmune (€16.7m).
Operating expenses amounting to €39.4m (€37.1m for the first half of 2017), of which 86% are related to research and development.
R&D expenses were up €4.6m during the periods under review, in line with the broadening and progress of Innate’s pipeline.Share-based payments were down €4.0m, including €1.9m in R&D and €2.1m in G&A, making up the most of G&A expenses decrease.
A net loss for the first half of 2018 amounting to €16.2m (€16.6m for the first half of 2017).

On September 14, 2018 EpimAb Biotherapeutics, an emerging Shanghai-based biopharmaceutical company specializing in bispecific antibodies, reported that it has filed an IND for its most advanced therapeutic development candidate EMB01 (Press release, EpimAb Biotherapeutics, SEP 14, 2018, View Source [SID1234529512]). The applications were simultaneously submitted to the U.S. Food and Drug Administration (FDA) and the National Medical Products Administration (NMPA) in China to investigate the treatment of solid tumors with EpimAb’s novel bispecific antibody.

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"Advancing our first compound into the clinic just three years after founding the company is a significant and transformational milestone for EpimAb," commented Chengbin Wu, PhD, CEO and founder of EpimAb Biotherapeutics. "This achievement proves that our FIT-Ig technology delivers bispecific antibodies with drug-like properties and manufacturing efficiency that can rapidly be advanced into clinical trials. We are now eager to learn how these novel drug candidates can impact patients’ lives."

EMB01 is a bispecific antibody based on EpimAb’s proprietary FIT-Ig (Fabs-In-Tandem Immunoglobulin) technology to generate bispecific molecules with superior properties. EMB01 simultaneously targets two receptors, which are widely expressed on cancer cells, EGFR and cMET, with a unique and synergistic mechanism and has shown significant and long-lasting activity in multiple preclinical solid tumor models. EpimAb initiated formal preclinical development in May 2017 and since then successfully completed all requirements for IND filing.

While EMB01 is progressing towards the clinic, EpimAb is advancing several biologics creating a proprietary pipeline based on its FIT-Ig platform. These earlier-stage assets are focused on immuno-oncology approaches in areas of high medical need in cancer.

On September 14, 2018 AstraZeneca and MedImmune, its global biologics research and development arm, reported that the US Food and Drug Administration (FDA) has approved Lumoxiti (moxetumomab pasudotox-tdfk) for the treatment of adult patients with relapsed or refractory hairy cell leukaemia (HCL) who have received at least two prior systemic therapies, including treatment with a purine nucleoside analog (Press release, AstraZeneca, SEPT 14, 2018, View Source [SID1234529431]). Lumoxiti is not recommended in patients with severe renal impairment (CrCl ≤ 29 mL/min).2 The Phase III trial results demonstrated 75% (95% confidence interval [CI]: 64, 84) of patients receiving Lumoxiti achieved an overall response; 30% (95% CI: 20, 41) had a durable complete response.2,3

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Dave Fredrickson, Executive Vice-President, Global Head Oncology Business Unit, said: "Today’s FDA approval of Lumoxiti represents a significant milestone for people living with hairy cell leukaemia, a rare blood cancer that can result in serious and life-threatening conditions. For patients, this approval provides the first FDA-approved medicine for this condition in more than 20 years."

Robert J. Kreitman, MD, Senior Investigator, Head of Clinical Immunotherapy Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, and Principal Investigator of the Phase III clinical trial, said: "While many patients with hairy cell leukaemia experience a remission with current treatments, 30% to 40% will relapse five to ten years after their first treatment.4 With subsequent treatments, durations of response diminish and toxicities accumulate, and few approved treatment options exist.5,6 Moxetumomab pasudotox represents a promising non-chemotherapeutic agent for HCL, addressing an unmet medical need for physicians and their patients."

Lumoxiti was approved under FDA Priority Review.7 The approval is based on data from the Phase III single-arm, open-label ‘1053’ trial of Lumoxiti monotherapy in 80 patients who have received at least two prior therapies, including a purine nucleoside analog.3 The primary endpoint of the trial was durable complete response.3 Summary of key results from the trial, as determined by a blinded independent central review:2

Efficacy measure

Result %, (95% CI)

Durable complete response ratea,b

30% (20, 41)

Overall response ratec

75% (64, 84)

Complete response rated

41% (30, 53)

Partial response ratee

34% (24, 45)

Haematologic remission rateb

80%

a Durable complete response is defined as patients who achieved complete response with haematologic remission for a duration of more than 180 days

b Haematologic remission is defined as haemoglobin > 11g/dL, neutrophils > 1500/mm3, platelets > 100,000/mm3 without transfusions or growth factor for at least 4 weeks

c Overall response rate is defined as best overall response of complete response or partial response

d Complete response is defined as clearing of the bone marrow of hairy cells by routine haematoxylin and eosin stain, radiologic resolution of pre-existing lymphadenopathy and/or organomegaly, and haematologic remission

e Partial response is defined as ≥ 50% decrease or normalisation (< 500/mm3) in peripheral blood lymphocyte count, reduction of pre-existing lymphadenopathy and/or organomegaly, and haematologic remission

The median time to haematologic remission was 1.1 months (range: 0.2 to 13).2 At data cut-off, the median duration of complete response was not yet reached after a median 16.7 months of follow-up.2

Capillary leak syndrome (CLS) and haemolytic uraemic syndrome (HUS), including life-threatening cases of each, have been reported among patients treated with Lumoxiti. In the combined safety database of 129 HCL patients treated with Lumoxiti, Grade 3 or 4 CLS occurred in 1.6% and 2% of patients, respectively. Grade 3 or 4 HUS occurred in 3% and 0.8% of patients, respectively.2

In the ‘1053’ trial of 80 patients, the most common Grade 3 or 4 adverse reactions (reported in at least ≥ 5% of patients) were hypertension, febrile neutropenia, and HUS. HUS was the most common adverse reaction leading to discontinuation (5%). The most common adverse reactions (≥ 20%) of any grade were infusion related reactions (50%), oedema (39%), nausea (35%), fatigue (34%), headache (33%), pyrexia (31%), constipation (23%), anaemia (21%), and diarrhoea (21%). The most common laboratory abnormalities (≥ 20%) of any grade were creatinine increased, ALT increased, hypoalbuminaemia, AST increased, hypocalcaemia, hypophosphataemia, haemoglobin decreased, neutrophil count decreased, hyponatreamia, blood bilirubin increased, hypokalaemia, GGT increased, hypomagnesaemia, platelet count decreased, hyperuricaemia, and alkaline phosphate increased.2

The recommended dose of Lumoxiti is 0.04 mg/kg administered as an intravenous infusion over 30 minutes on days 1, 3, and 5 of each 28-day cycle up to 6 cycles, disease progression, or unacceptable toxicity.2

Notes to Editors
About hairy cell leukaemia

Hairy cell leukaemia (HCL) is a rare, chronic, and slow-growing leukaemia in which the bone marrow overproduces abnormal B cell lymphocytes.8,9 HCL can result in serious and life-threatening conditions, including infections, bleeding and anaemia.10 Approximately 1,000 people are diagnosed with HCL in the US each year.11 While many patients initially respond to treatment, 30% to 40% will relapse five to ten years after their first treatment.4 With no established standard of care and very few treatments available, there remains significant unmet medical need for people with relapsed or refractory HCL.4,8

About Lumoxiti

Lumoxiti (moxetumomab pasudotox, formerly CAT8015 or HA22) is a CD22-directed cytotoxin and a first-in-class treatment in the US for adult patients with relapsed or refractory hairy cell leukaemia (HCL) who have received at least two prior systemic therapies, including treatment with a purine nucleoside analog. Lumoxiti is not recommended in patients with severe renal impairment (CrCl ≤ 29 mL/min).2 It comprises the CD22 binding portion of an antibody fused to a truncated bacterial toxin; the toxin inhibits protein synthesis and ultimately triggers apoptotic cell death.2 Lumoxiti has been granted Orphan Drug Designation by the FDA for the treatment of HCL.

About the ‘1053’ Phase III trial

The ‘1053’ trial is a single-arm, multicentre Phase III clinical trial assessing the efficacy, safety, immunogenicity and pharmacokinetics of moxetumomab pasudotox monotherapy in patients with relapsed or refractory HCL who have received at least two prior therapies, including one purine nucleoside analog. The trial was conducted in 80 patients across 34 sites in 14 countries. The primary endpoint was durable complete response (CR), defined as CR with haematologic remission (blood count normalisation) for >180 days. Secondary outcome measures included overall response rate, relapse free survival, progression-free survival, time to response, safety, pharmacokinetic and immunogenic potential.7

Early discovery of moxetumomab pasudotox was led by the National Cancer Institute (NCI). The collaboration between NCI and MedImmune, AstraZeneca’s global biologics research and development arm, is an example of how scientific partnerships can lead to important advances for cancer patients.