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On December 11, 2017 Oscotec reported that shares of Oscotec rebounded on the company’s announcement that it has launched a clinical trial in the U.S. on SKI-G-801, a treatment for acute myeloid leukemia (AML) (Press release, Oscotec, DEC 11, 2017, View Source [SID1234573544]).

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The biotech company said in a public regulatory filing on Monday that its phase-1 clinical trial on SKI-G-801 will begin at six U.S. hospitals.

Oscotec’s shares, which had slid since Dec. 4, rebounded to 10,250 won ($9.4) as of noon on Monday, up 150 won from the previous trading day. Compared with early this year’s stock price of 7,390 won per share, it was up 38 percent.

SKI-G-801 is a treatment that selectively inhibits fms-like tyrosine receptor kinase 3 (FLT3). The company hopes that the new drug candidate will lower side effects and recurrence rate, compared to existing chemotherapies.

The U.S. study will check safety and drug tolerance, after administering SKI-G-801 to recurring or non-reacting AML patients and raising doses in a phased way. The trial will also test the drug’s appropriate doses and efficacy in AML patients with FLT3 mutations.

"Compared to the existing FLT3 inhibitors, SKI-G-801 has excellent pharmacologic activation and long-acting efficacy. Besides, we confirmed its efficacy on FLT3 mutations, which existing inhibitors had no effectiveness, as well as in the drug-resistant environment," Oscotec said.

It went on to say,"If we confirm the safety, drug tolerance, and oncolytic efficacy in the clinical trial, we expect that we will be able to transfer our technology to a multinational pharmaceutical company."

In July 2015, Oscotec transferred its investigational non-small cell lung cancer therapy YH25448 to Yuhan Corp. under an income-sharing contract.

Oscotec’s revenue reached 3.25 billion won ($2.99 million) in the first three quarters this year, with an operating loss of 992 million won.

Its flagship product is InduCera, a material for bone transplant, which takes up about 30 percent of the total sales.

On December 11, 2017 Italfarmaco Group, a specialty pharmaceutical company, reported the positive results from two clinical trials evaluating its proprietary histone deacetylase (HDAC) inhibitor givinostat in Polycythemia Vera patients -Italfarmaco Group, a specialty pharmaceutical company, reported the positive results from two clinical trials evaluating its proprietary histone deacetylase (HDAC) inhibitor givinostat in Polycythemia Vera patients. The data were presented in an oral and a poster presentation on Saturday December 9th, 2017 at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting & Exposition held in Atlanta, Georgia. In the oral presentation, the company discussed positive safety and efficacy data from a two-part study of givinostat in which over 80% of patients responded to the treatment. These results were further supported by a poster presentation of a long-term evaluation of givinostat’s effect in patients over four years. Combined, the data provide a basis for the company’s decision to proceed with a pivotal Phase III trial in this indication. Polycythemia Vera is a rare blood disease characterized by an increased number of red blood cells, white blood cells and platelets, which significantly raises the risk for thromboembolic and hemorrhagic complications.

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"Polycythemia Vera patients have limited treatment options that currently only ameliorate the symptoms of the disease. We look forward to initiating the planned pivotal study in this indication."
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In the oral presentation at ASH (Free ASH Whitepaper), the principal investigator described the multi-center, open label Phase Ib/II givinostat study, which included a dose-escalation and an evaluation of preliminary efficacy and tolerability. The data demonstrated that givinostat was well tolerated overall at the defined dose of 100 mg twice daily and the majority of adverse events were mild to moderate in severity. The overall response rate was more than 80% according to European Leukemia Net standard response criteria, which measure a range of parameters including reduction of the size of spleen and liver, peripheral blood count, absence of hemorrhagic and thrombotic events and bone marrow analysis.

In the larger study investigating long-term safety and efficacy, Italfarmaco researchers and collaborators presented data supporting the potential of givinostat as a durable treatment option that reduces the symptoms and underlying risks of the disease while remaining well-tolerated. Overall, 80% of patients maintained at least a partial response for more than four years. After four years of treatment no patient reported microvascular symptoms or headaches. Pruritus (itchiness), one of the typical symptoms of Polycythemia Vera, was absent in 67% of the patients. Furthermore, the overall incidence of thrombosis (1.13% patients per year) was reduced in comparison to the expected incidence rate in this patient population (3% patients/year). Givinostat treatment additionally reduced the levels of mutated Janus Kinase 2 (JAK2), a key underlying cause of the disease, by 25% in over 40% of the patients.

"The givinostat Phase II proof-of-concept and long-term data are very encouraging and demonstrate the potential of this compound to address the underlying mechanism of the disease while remaining well-tolerated," said Dr. Paolo Bettica, Vice President Research and Development. "Polycythemia Vera patients have limited treatment options that currently only ameliorate the symptoms of the disease. We look forward to initiating the planned pivotal study in this indication."

"Italfarmaco is particularly gratified that these results were selected for presentation at ASH (Free ASH Whitepaper) because they underscore the value of our internal research and development efforts," added Dr. Francesco De Santis, President of Italfarmaco.

About Polycythemia Vera

Polycythemia Vera is a rare blood disease characterized by an overproduction of red blood cells, white blood cells and platelets, which thickens the blood and increases the risk of blood clots, a major underlying cause of life-threatening conditions such as thrombosis, embolisms, heart attack or stroke. The disease is associated with mutations in the Janus Kinase 2 (JAK2) gene and disease-related symptoms include headaches, itching and microvascular symptoms. The current standard of care ranges from phlebotomy alone or in combination with low-dose aspirin, to drugs such as the cytoreductive hydroxycarbamide or the JAK inhibitor ruxolitinib. These reduce symptoms, but no treatments targeting the underlying disease mechanism are available.

About Givinostat

Givinostat is a potent, orally-available, class I and II histone deacetylase (HDAC) inhibitor and an investigational product discovered through Italfarmaco’s internal research and development efforts. Through the pharmacological modulation of cell growth, differentiation and apoptosis and the additional specific inhibition of the proliferation of cells bearing the JAK2V617F mutation, givinostat may represent a novel disease modifier in Polycythemia Vera. Besides these properties, givinostat has shown immuno-modulatory activity that may specifically target other diseases, making it a very promising candidate for Duchenne Muscular Dystrophy (Phase III) and Becker Muscular Dystrophy (Phase II). The data were presented in an oral and a poster presentation on Saturday December 9th, 2017 at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting & Exposition held in Atlanta, Georgia. In the oral presentation, the company discussed positive safety and efficacy data from a two-part study of givinostat in which over 80% of patients responded to the treatment. These results were further supported by a poster presentation of a long-term evaluation of givinostat’s effect in patients over four years. Combined, the data provide a basis for the company’s decision to proceed with a pivotal Phase III trial in this indication. Polycythemia Vera is a rare blood disease characterized by an increased number of red blood cells, white blood cells and platelets, which significantly raises the risk for thromboembolic and hemorrhagic complications.

"Polycythemia Vera patients have limited treatment options that currently only ameliorate the symptoms of the disease. We look forward to initiating the planned pivotal study in this indication."
Tweet this
In the oral presentation at ASH (Free ASH Whitepaper), the principal investigator described the multi-center, open label Phase Ib/II givinostat study, which included a dose-escalation and an evaluation of preliminary efficacy and tolerability. The data demonstrated that givinostat was well tolerated overall at the defined dose of 100 mg twice daily and the majority of adverse events were mild to moderate in severity. The overall response rate was more than 80% according to European Leukemia Net standard response criteria, which measure a range of parameters including reduction of the size of spleen and liver, peripheral blood count, absence of hemorrhagic and thrombotic events and bone marrow analysis.

In the larger study investigating long-term safety and efficacy, Italfarmaco researchers and collaborators presented data supporting the potential of givinostat as a durable treatment option that reduces the symptoms and underlying risks of the disease while remaining well-tolerated. Overall, 80% of patients maintained at least a partial response for more than four years. After four years of treatment no patient reported microvascular symptoms or headaches. Pruritus (itchiness), one of the typical symptoms of Polycythemia Vera, was absent in 67% of the patients. Furthermore, the overall incidence of thrombosis (1.13% patients per year) was reduced in comparison to the expected incidence rate in this patient population (3% patients/year). Givinostat treatment additionally reduced the levels of mutated Janus Kinase 2 (JAK2), a key underlying cause of the disease, by 25% in over 40% of the patients.

"The givinostat Phase II proof-of-concept and long-term data are very encouraging and demonstrate the potential of this compound to address the underlying mechanism of the disease while remaining well-tolerated," said Dr. Paolo Bettica, Vice President Research and Development. "Polycythemia Vera patients have limited treatment options that currently only ameliorate the symptoms of the disease. We look forward to initiating the planned pivotal study in this indication."

"Italfarmaco is particularly gratified that these results were selected for presentation at ASH (Free ASH Whitepaper) because they underscore the value of our internal research and development efforts," added Dr. Francesco De Santis, President of Italfarmaco.

About Polycythemia Vera

Polycythemia Vera is a rare blood disease characterized by an overproduction of red blood cells, white blood cells and platelets, which thickens the blood and increases the risk of blood clots, a major underlying cause of life-threatening conditions such as thrombosis, embolisms, heart attack or stroke. The disease is associated with mutations in the Janus Kinase 2 (JAK2) gene and disease-related symptoms include headaches, itching and microvascular symptoms. The current standard of care ranges from phlebotomy alone or in combination with low-dose aspirin, to drugs such as the cytoreductive hydroxycarbamide or the JAK inhibitor ruxolitinib. These reduce symptoms, but no treatments targeting the underlying disease mechanism are available.

About Givinostat

Givinostat is a potent, orally-available, class I and II histone deacetylase (HDAC) inhibitor and an investigational product discovered through Italfarmaco’s internal research and development efforts. Through the pharmacological modulation of cell growth, differentiation and apoptosis and the additional specific inhibition of the proliferation of cells bearing the JAK2V617F mutation, givinostat may represent a novel disease modifier in Polycythemia Vera. Besides these properties, givinostat has shown immuno-modulatory activity that may specifically target other diseases, making it a very promising candidate for Duchenne Muscular Dystrophy (Phase III) and Becker Muscular Dystrophy (Phase II).

On December 11, 2017 Syntimmune presented Poster Presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting, Atlanta, Georgia (Press release, Syntimmune, DEC 11, 2017, View Source [SID1234522534]).

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On December 11, 2017 TG Therapeutics, Inc. (NASDAQ:TGTX), reported the presentation of six posters highlighting preclinical and clinical data sets for TGR-1202 (umbralisib), the Company’s once-daily PI3K delta inhibitor, and TG-1101 (ublituximab), the Company’s novel glycoengineered anti-CD20 monoclonal antibody, at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting, currently being held at the Georgia World Congress Center in Atlanta, Georgia (Press release, TG Therapeutics, DEC 11, 2017, View Source [SID1234522557]).

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, stated, "We are very pleased by the data presented yesterday and today during the ASH (Free ASH Whitepaper) annual meeting. The preclinical data help us to better understand the difference between TGR-1202 and other agents in the class and offers a more complete rationale for the differentiated safety profile seen in the clinic. With the updated and expanded integrated safety analysis of TGR-1202 alone and in combination with other agents, we believe we have provided the long-term follow-up sufficient to allay any lingering safety concerns related to TGR-1202 caused by the toxicity profile of first generation PI3K delta inhibitors." Mr. Weiss continued, "In 2018, with registration-directed data expected in CLL and NHL, our focus will turn to showcasing the efficacy of TGR-1202 and our proprietary combination of TG-1101 plus TGR-1202, our U2 combination, ideally leading to NDA/BLA filings in CLL and NHL."

The following summarizes the highlights from each poster presented at the ASH (Free ASH Whitepaper) 2017 meeting.

Clinical Data Presentations:

An Integrated Safety Analysis of the Next Generation PI3K Delta Inhibitor Umbralisib (TGR-1202) in Patients with Relapsed/Refractory Lymphoid Malignancies

This presentation includes data that were pooled from 5 completed or ongoing Phase 1 or 2 studies containing TGR-1202, including a total of 347 patients with relapsed or refractory hematologic malignancies. Patients were heavily pretreated, with 50% of patients having seen 3 or more prior lines of therapy.

Highlights from this poster include:

● 347 patients have been treated with TGR-1202 across the 5 studies in this pooled analysis, with median duration of exposure of 6.5 months, and 176 patients on drug for 6+ months, 104 patients for 12+ months, with the longest patients on daily TGR-1202 for 4+ years
● In longer follow-up and in an expanded patient population, TGR-1202 exhibits a differentiated safety profile compared to prior generation PI3K delta inhibitors
● Discontinuations due to adverse events (AEs) were rare at under 10% for all studies
● Grade 3/4 AEs commonly associated with PI3K delta inhibitors have been rare, with pneumonitis (< 0.5%), transaminitis (~2%) and colitis (< 1%), the latter occurring with no apparent association to time on therapy
● Improved tolerability with few discontinuations due to AEs has allowed patients to remain on continuous dosing to achieve and sustain promisingly high rates of response:
o 85% Overall Response Rate (ORR) for single agent TGR-1202 in relapsed/refractory Chronic Lymphocytic Leukemia (CLL)
o 53% ORR for single agent TGR-1202 in relapsed/refractory Follicular Lymphoma (FL)

KI Intolerance Study: A Phase 2 Study to Assess the Safety and Efficacy of Umbralisib (TGR-1202) In Patients with Chronic Lymphocytic Leukemia (CLL) Who Are Intolerant to Prior BTK or PI3K-delta Inhibitor Therapy (Abstract Number 4314)

This poster presentation includes data from patients with CLL who are intolerant to prior BTK or PI3K delta inhibitor therapy who were then treated with single agent TGR-1202. To be eligible for the study patients had to have received prior treatment with a BTK inhibitor (ibrutinib, acalabrutinib) or a PI3K delta inhibitor (idelalisib, duvelisib) and discontinued therapy due to intolerance within 12 months of starting treatment on this study. Thirty-three patients were evaluable for safety (30 patients with ibrutinib intolerance, and 3 patients with idelalisib intolerance) of which 32 were evaluable for efficacy (1 patient had a confirmed Richter’s Transformation (RT) at enrollment which did not meet eligibility criteria). TGR-1202 appears to demonstrate a favorable safety profile in patients intolerant to prior ibrutinib or idelalisib, with only 2 patients (6%) discontinuing due to an adverse event, neither of which was a recurrent AE from prior TKI therapy.

Highlights from this poster include:

● 94% (30 of 32) of patients remain progression-free
● Median time on study at the data cut off was approximately 6 months with the majority of patients continuing on study and follow-up ongoing
● No patient discontinued TGR-1202 due to a recurrent AE which led to discontinuation from their prior kinase inhibitor

Phase I/II Study of Pembrolizumab in Combination with Ublituximab (TG-1101) and Umbralisib (TGR-1202) in Patients with Relapsed/Refractory CLL (Abstract Number 3010)

This presentation includes data from patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) or Richter’s Transformation (RT) treated with the triple combination of TG-1101, TGR-1202, and pembrolizumab. Eleven patients were evaluable for safety (9 CLL patients and 2 RT patients) and 10 were evaluable for efficacy (9 CLL and 1 RT), with one patient too early to evaluate.

Highlights from this poster include:

● One AE of increased LFTs was observed which met criteria for DLT; patient was re-challenged and remains on study treatment with TGR-1202 maintenance now 15+ months
● 78% (7 of 9) ORR in patients with relapsed/refractory CLL
● 75% (3 of 4) ORR in BTK refractory CLL patients
● Responses have been durable with the first patient progression-free for 24+ months

Preclinical Data Presentations:

Differential Regulation of T Cells By PI3K Delta Inhibitors in a CLL Murine Model (Abstract Number: 3009)

This poster presentation included preclinical data describing the differential regulation of human T cells by TGR-1202 in a preclinical CLL murine model.

Highlights from this poster include:

● TGR-1202 oral treatment induced less incidence of toxicity in CLL mice compared to other PI3K delta inhibitors
● TGR-1202 relatively preserved Treg quantity and function in a dose dependent manner compared to other PI3K delta inhibitors in normal and murine CLL T cells
● Inhibition of casein-kinase 1 epsilon (CK1e) by TGR-1202 may explain the relative preservation of Treg cells in these in-vivo models

Umbralisib/TGR-1202 As a Novel Dual PI3K/CK1 Inhibitor Has a Unique Therapeutic Role in Silencing Oncogenes in Aggressive Lymphomas (Abstract Number 2809)

This poster presentation expanded on existing preclinical data demonstrating that TGR-1202 is synergistic with carfilzomib in certain aggressive lymphoma cell lines.

Highlights from this poster include:

● TGR-1202 is highly synergistic with the proteasome inhibitor carfilzomib in cell line models of double hit lymphoma and mantle cell lymphoma
● Based on this preclinical work, a Phase 1 clinical study to evaluate the safety and efficacy of TGR-1202 in combination with carfilzomib is currently enrolling patients

PI3K Delta Inhibitors Induce Primary Monocyte Cytotoxicity but Do Not Alter Monocyte Differentiation (Abstract Number 4284)

This poster presentation included preclinical data exploring the effect of PI3K delta inhibitors on monocyte activity.

Highlights from this poster include:

● The clinical benefit and initial lymphocytosis seen with PI3K delta inhibitors in CLL may be related in part to direct effects on monocyte derived cells
● Idelalisib and TGR-1202 differed in the extent of monocyte cytotoxicity induced and inhibition of pAKT
● The direct effects of PI3K delta inhibitors on monocytes suggests these drugs may have efficacy beyond B-cell malignancies, including in monocytic neoplasms or other malignancies with monocyte derived cells in the tumor microenvironment

The above referenced presentations, are available on the Publications page of the Company’s website at www.tgtherapeutics.com.