On June 20, 2015 Epizyme reported results from the ongoing phase 1 trial of tazemetostat (EPZ-6438), a first-in-class EZH2 inhibitor, showing meaningful clinical activity when used as an oral monotherapy in patients with advanced B-cell non-Hodgkin lymphomas (NHL) and solid tumors (Press release, Epizyme, JUN 20, 2015, View Source [SID:1234505786]). In NHL, treatment with tazemetostat continues to demonstrate an encouraging profile with nine of 15 evaluable NHL patients achieving an objective response, including a partial response in the first treated patient with an EZH2 tumor mutation. The data, which include patients from the dose escalation and dose expansion cohorts of the phase 1 study, as well as a food effects sub-study, were presented today by Vincent Ribrag, M.D., Institut Gustave Roussy, at the 13th International Conference on Malignant Lymphoma.

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"The breadth, depth and durability of responses seen in NHL patients among multiple histologies continue to impress, as does the safety and tolerability of tazemetostat in this phase 1 study," said Dr. Ribrag. "Among the patients in the dose escalation cohorts, we have seen a noteworthy deepening of responses over time, and in the first treated patient with an EZH2 tumor mutation, we have seen a partial response, which is very encouraging."

Summary Results

As of June 8, 2015, the following clinical data were observed:

Nine of 15 evaluable NHL patients have achieved an objective response, including two patients with an ongoing complete response (CR).

Five of nine evaluable diffuse large B-cell lymphoma (DLBCL) patients achieved an objective response. One patient with a CR remains on study at 18 months of treatment.

Three of five evaluable patients with follicular lymphoma achieved an objective response. One patient with a CR remains on study at 13 months, and one patient with a PR remains on study at 13 months.

One patient with a marginal zone lymphoma achieved a partial response and continues on study at 11 months.

All treatment responses were observed between two and 10 months on therapy.

One of 14 patients evaluated for EZH2 status possesses a specific EZH2 tumor mutation (Y646H). This patient, who had relapsed or been refractory to six previous treatment regimens, achieved a partial response after 16 weeks of therapy and remains on study.

The majority of adverse events were grade 1 or grade 2 within the evaluable for safety population of 45 patients with NHL and solid tumors. The most common adverse events regardless of attribution were asthenia, anorexia, anemia, dyspnea and nausea. Five grade 3 or greater treatment-related adverse events were observed including one each of: grade 3 anorexia, grade 3 hypertension, grade 3 transaminase elevation, grade 4 thrombocytopenia, and grade 4 neutropenia.

"These results highlight the therapeutic potential of tazemetostat in NHL, with a number of patients achieving durable remissions with time on treatment at or beyond one year," said Peter Ho, M.D., Ph.D., Chief Development Officer, Epizyme. "We look forward to exploring further the clinical utility of tazemetostat in NHL in a robust phase 2 development program."

The NHL patients enrolled on study were heavily pre-treated, with 85 percent of patients having received three or more prior therapies and 37 percent of patients having received more than five or more prior therapies. Thirty-seven percent of patients were refractory to their last prior regimen and 26 percent of patients had received a prior autologous hematopoietic stem cell transplant.

Drug pharmacokinetics showed rapid absorption with a mean terminal half-life of three to five hours. Cmax and AUC1-12hr were dose proportional at steady-state throughout the dosing range. Steady-state Ctrough levels were reached by day 15.

The company plans to report a further update from the phase 1 trial by the end of 2015.

Study Design

This open-label, multi-center, phase 1 study is investigating tazemetostat as monotherapy in patients with relapsed or refractory B-cell non-Hodgkin lymphomas or advanced solid tumors. The study objectives include identification of the recommended phase 2 dose or maximum tolerated dose, safety, tolerability, pharmacokinetics and preliminary evaluation of anti-tumor activity. Five cohorts were studied in the dose escalation phase: 100 mg, 200 mg, 400 mg, 800 mg and 1600 mg; and two cohorts, 800 mg and 1600 mg, were evaluated in the dose expansion phase. All doses were given twice daily.

Expanded Tazemetostat Phase 2 Plans

Epizyme is now enrolling patients in an international five-arm, multi-center, phase 2 study during the second quarter of 2015 that will assess the safety and efficacy of tazemetostat in patients with relapsed or refractory NHL, stratified by cell of origin and EZH2 mutation status. A second planned phase 2 trial of tazemetostat in adult patients with INI1-deficient solid tumors is expected to begin later in 2015. Patients in both studies will be treated with the recommended phase 2 dose of 800 mg twice daily. A phase 1 study in pediatric patients with INI1-deficient solid tumors is also expected to start later in 2015.

In addition to these previously announced studies, the company plans to initiate additional trials of tazemetostat, including:

A combination study of tazemetostat with R-CHOP in patients with DLBCL. R-CHOP, which represents current first-line treatment for patients with DLBCL, is comprised of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.
A combination study of tazemetostat with a B-cell signaling agent or other emerging targeted therapies for B-cell lymphomas.
"Conducting combination studies in B-cell lymphoma will further elucidate the clinical potential of tazemetostat," said Dr. Ho. "Scientists here at Epizyme have demonstrated pre-clinical synergy with both current standard-of-care therapeutics and emerging investigational agents, and we believe that tazemetostat has a safety and tolerability profile that will lend itself well to combination regimens."

About EZH2 in Cancer

EZH2 is a histone methyltransferase (HMT) that is increasingly understood to play a potentially oncogenic role in a number of cancers. These include non-Hodgkin lymphomas, INI1-deficient cancers such as malignant rhabdoid tumors, epithelioid sarcomas and synovial sarcoma; and a range of other solid tumors.

About Tazemetostat

Epizyme is developing tazemetostat for the treatment of non-Hodgkin lymphoma patients and patients with INI1-deficient solid tumors. Tazemetostat is a first-in-class small molecule inhibitor of EZH2 created by Epizyme using its proprietary product platform. In many human cancers, aberrant EZH2 enzyme activity results in misregulation of genes that control cell proliferation resulting in the rapid and unconstrained growth of tumor cells. Tazemetostat is the WHO International Non-Proprietary Name (INN) for EPZ-6438.

Tazemetostat is the second HMT inhibitor to enter human clinical development (following Epizyme’s DOT1L inhibitor, pinometostat, also known as EPZ-5676).

Additional information about this program, including clinical trial information, may be found here: View Source

On June 19, 2015 PlasmaTech Biopharmaceuticals, Inc. (NASDAQ: PTBI), a biopharmaceutical company focused on developing and delivering gene therapy and plasma-based products for severe and life-threatening rare diseases, reported a name change to Abeona Therapeutics, Inc. to reflect its broader rare disease commitment (Press release, Abeona Therapeutics, JUN 19, 2015, View Source;p=irol-newsArticle&ID=2060889 [SID:1234510405]). The Company expects that its common stock will begin trading on NASDAQ on Monday, June 22, under the ticker symbol ABEO, along with announcing Abeona Therapeutics to ring the Nasdaq Stock market closing bell on Monday, June 22nd at 4:00 pm ET. Live streaming can be found at: View Source)

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"Abeona was forged from the company’s close collaborations with key stakeholders, all dedicated to transforming new biotechnology insights into breakthrough treatments for rare diseases," stated Steven Rouhandeh, Executive Chairman. "Most importantly, we have established a dedicated team of world class professionals led by Dr. Tim Miller, who will be critical to building and accelerating value for patients and shareholders."

A rare disease is one that affects fewer than 200,000 people in the United States. There are nearly 7,000 rare diseases, which may involve chronic illness, disability, and often, premature death. More than 25 million Americans and 30 million Europeans have a rare disease. While rare diseases can affect any age group, about 50% of people affected are children (15 million); and rare diseases account for 35% of deaths in the first year of life. These rare diseases are often poorly diagnosed, very complex, and have no treatment or not very effective treatment — over 95% of rare diseases do not have a single FDA or EMA approved drug treatment. However, most rare diseases are often caused by changes in genes — 80% are genetic in origin and can present at any stage of life.

"Effectively developing therapies for rare disease requires innovative approaches and strong collaboration between researchers, industry, regulators and patient groups," noted Tim Miller, Ph.D., President & CEO. "We believe emerging insights in gene therapy and advances in biotechnology provide significant opportunities to develop breakthrough treatments for rare diseases. Our focus is transforming the promise of our products and platforms into new treatments for severe and life-threatening rare diseases such as Sanfilippo syndromes types A and B, juvenile Batten disease, and Fanconi anemia."

About the Abeona Name Change: Abeona (pronounced ey-bee-ohn-uh) is the Roman Goddess who protects children as they take their first steps away from home.

On June 18, 2015 Varian Medical Systems reported that it has entered into a multi-year agreement with Inova to be its exclusive supplier of advanced technology for image-guided, high-precision radiotherapy and radiosurgery (Press release, InfiMed, JUN 18, 2015, View Source [SID:1234505459]). Inova, a not-for-profit healthcare system operating five hospitals in Northern Virginia, will also install Varian software across its sites, as part of a long-term plan to create an integrated informatics system and to unify cancer care across its network.

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Under the agreement, Inova will acquire multiple Varian TrueBeam radiotherapy/ radiosurgery systems over nine years, with initial replacements at Inova’s Alexandria and Loudoun Hospitals. TrueBeam technology offers clinicians tremendous versatility in choosing and administering different types of radiation treatment for each patient as appropriate, from intensity-modulated radiotherapy to stereotactic radiosurgery. These treatments can be delivered with greater time efficiency—and hence cost effectiveness—than is possible with many other radiotherapy systems.

Inova will also expand its deployment of Varian’s ARIA information management and Eclipse treatment planning software, currently in use at two of the five sites, across the Inova network, and add Varian’s new InSightive software for data analytics.

"We have been managing radiation oncology departments at two of our sites using Varian software for some time," said says Gopal K. Bajaj, MD, Chairman and Medical Director of Radiation Oncology, Inova. "We will replace competitive solutions at the other sites in order to unify cancer care across the system. We like the fact that ARIA is a comprehensive system that consolidates all treatment data in a single database. It dovetails with our plans to integrate all of our cancer treatment services in support of better care coordination and closer collaboration among clinical team members."

Inova will also deploy Varian’s InSightive software for data analytics, which will enable clinicians and administrators to mine the enormous amount of data housed within the ARIA oncology information system database.

"ARIA is a robust practice management system and electronic medical record with a tremendous amount of information that Inova can mine and analyze to enhance the quality of care and the efficiency of its clinical operations," says Sukhveer Singh, vice president of Varian’s Oncology Continuum Solutions. "ARIA includes many interfaces for importing data from other hospital information systems, resulting in a very rich resource. InSightive Analytics provides access to this data, making it visible and useful."

"Our partnership with Varian will help as we create an integrated healthcare delivery system that uses knowledge-based approaches for the optimal benefit of patients," adds Donald Trump, MD, CEO of the Inova Dwight and Martha Schar Cancer Institute. "We will study the data from cancer patients across our network, including detailed information regarding patient characteristics as well from a detailed study of patients’ tumor tissue and their own genetic makeup, ultimately to analyze why different patients react differently to the same treatments. Varian’s ARIA and Insightive informatics will help us aggregate and analyze that data, and tease out actionable information for the benefit of our patients."

The total value of the multi-year agreement is estimated at $25 million inclusive of products and services, such as turnkey hardware and software support. Varian booked approximately $4 million of this amount during the third quarter of fiscal year 2015. The remainder of the order will be booked in accordance with the company’s policies over the term of the agreement.

On June 18, 2016 TFS Corporation Limited ("TFS", "Company", ASX: TFC), the world’s largest owner and manager of commercial Indian sandalwood plantations, reported it has entered into share purchase agreements to acquire US-based pharmaceutical partners ViroXis Corporation ("ViroXis") and Santalis Pharmaceuticals ("Santalis", together "the Acquisitions") (Press release, TFS, JUN 18, 2015, View Source [SID1234517229]).

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TFS Chief Executive Officer Frank Wilson said, "The Acquisitions will extend TFS’s soil to oil strategy by expanding the Company’s vertically integrated business model. TFS will benefit from direct ownership of the pharmaceutical companies which exclusively develop and sell products containing TFS-grown and processed Indian sandalwood oil to the high-value pharmaceutical sector."

"While TFS previously benefited from pharmaceutical product development through oil sales, with these Acquisitions we will also capture all of the future product earnings, including product royalties and licence fees, generated by ViroXis and Santalis, thereby significantly enhancing our own earnings," Mr Wilson said.

"We have been directly involved over the last five years in successfully building the first mover advantage established by ViroXis and Santalis. These transactions will allow us to work even closer with the product development teams and accelerate the establishment of a range of sandalwood-based dermatological products. With increased control of the formulation we also expect to generate additional revenue from our oil sales."

Santalis has already licensed a range of dermatological products that contain TFS-grown Indian sandalwood oil to Nestle-owned Galderma, a global dermatological company. The acne product Benzac Acne Solutions, which is the first to have been commercialised by Santalis, successfully debuted on US shelves earlier this year and is already available in around 25,000 stores through major US retail chains. Following these Acquisitions, each sale of the Benzac Acne Solutions range will directly generate royalty revenues for TFS in addition to existing oil sales.

"Over time we expect a series of products containing TFS’s Indian sandalwood oil to be distributed by pharmaceutical companies to worldwide markets," Mr Wilson said.

Transaction summary
Subject to certain conditions to completion, TFS will pay minimum consideration of US$23.4 million for the issued shares in ViroXis and Santalis it does not already own (100% and 50% respectively), payable by US$1.5 million in cash and US$21.9 million in TFS shares.

The scrip component of the minimum consideration will involve the issuance of around 15.3 million TFS shares at a price of AU$1.85 per share. TFS anticipates issuing around 12.6 million shares in July 2015 and the remaining 2.7 million shares in the period between 10 September 2015 and 31 July 2016. Around 9.1 million of the 12.6 million shares expected to be issued in July 2015 will be subject to lock up provisions (which range between six and thirty months).

The shares issued pursuant to the Acquisitions will be made utilising the Company’s available placement capacity under ASX listing rule 7.1.

The total maximum consideration payable by TFS consists of fixed minimum payments of US$23.4 million and contingent payments over time of up to US$221.5 million. The contingent consideration only becomes payable when the acquired companies achieve significant operating and commercial milestones (from the launch or approval of new pharmaceutical products containing Indian sandalwood oil) and significant operating cash inflows.

The structure of the Acquisitions is designed to ensure that the founders of ViroXis and Santalis, who will continue to operate the businesses, are closely aligned to the ongoing and long-term success of the companies and their products. Both founders will sign new employment contracts on completion.

"Total consideration is directly linked to ViroXis and Santalis successfully developing and selling additional pharmaceutical products to the healthcare market, as has been achieved with the Benzac range. We have structured the transaction with minimal upfront cash outlay, flexibility with cash and scrip payments, incentives to generate additional revenue and profit, and lock-up provisions, to provide maximum value to TFS shareholders," Mr Wilson said.

Since 2010, ViroXis and Santalis have invested over US$17 million in the development and commercialisation of pharmaceutical products containing Indian sandalwood oil.

The Acquisitions do not impact TFS’s previous guidance for FY15 of NPAT of at least $90 million. After absorbing transaction costs, TFS continues to expect cash EBITDA to increase year-on-year by approximately 10%. On a stand-alone basis, and excluding any benefit from higher Indian sandalwood oil sales, the Acquisitions are expected to be EPS dilutive in FY16.

Further details on the key terms of the transactions are provided in Appendix One.

Background on ViroXis and Santalis
ViroXis is a bio-pharmaceutical company focused on developing and commercialising innovative, proprietary, botanical pharmaceuticals derived from sandalwood oil, exclusively for viral conditions. ViroXis was cofounded by its Chief Executive Officer Ian Clements, who has more than 20 years of experience in the pharmaceutical and biotechnology industries.

Santalis is focused on developing and commercialising sandalwood products targeting all possible conditions outside of viral skin diseases (dermatological conditions such as acne, eczema, psoriasis, redness and sensitive skin). Santalis was founded in 2010 and is a 50-50 joint venture with TFS. Santalis is led by Chief Executive Officer Paul Castella, who co-founded Santalis with Mr Clements and was also a co-founder of ViroXis. Dr Castella has a Ph.D. in molecular biology and has founded and managed numerous biotechnology companies with a successful record of product development, regulatory approval and commercialisation.

ViroXis CEO Ian Clements said: "I am delighted we have reached this agreement with TFS, with their ongoing support enabling us to extend and accelerate development of products using Indian sandalwood oil to treat viral skin infections, such as common skin warts and Molluscum contagiosum."

Santalis CEO Paul Castella added: "We have achieved great success to date through our landmark agreements with Galderma and we will be able to build on this by working even more closely with TFS in developing and marketing our pipeline of dermatological products containing Indian sandalwood oil. Santalis successfully developed the Benzac acne products, which have now launched across the US, and is well advanced with numerous other products, including for eczema."
Further details on ViroXis and Santalis are provided in Appendix Two.
APPENDIX ONE
TRANSACTION DETAILS
Transaction details The minimum purchase price is US$23.4 million (ViroXis: US$18.4 million, Santalis: US$5.0 million).

The maximum purchase price over time is US$244.9 million (ViroXis: US$154.9 million, Santalis: US$90.0 million) if all milestones, base earn out thresholds and incentive and final earn out thresholds are met through to the eight year anniversary of completion.

The contingent consideration has been structured as follows:
Minimum purchase price
The fixed minimum purchase price for ViroXis is US$18.4 million, comprising cash of US$1.5 million and stock of US$16.9 million.
The fixed minimum purchase price for Santalis is US$5.0 million comprised fully of stock.
The TFS shares will be issued at AU$1.85 per share, being the volume weighted average price for TFS shares for the 30 trading days to 17 June 2015.
In relation to the fixed minimum purchase price, a total of 15.3 million shares is expected to be issued within the following time-frames and be subject to the following lock up periods: Stock issued in July 2015 and subject to no lock up period: 3.5 million Stock issued in July 2015 and subject to lock up period of between 6 and 30 months: 9.1 million Stock issued between September 2015 and July 2016 and subject to no lock up period: 2.7 million

Milestone payments
The purchase price for ViroXis will increase by a maximum of US$26.0 million if the following milestones are achieved within certain periods in up to five years after completion:
1. US$2.0 million on the launch of an over-the-counter ("OTC") product
2. US$4.0 million on the enrolment of the first patient in a Phase 3 FDA trial for a skin indication
3. US$4.0 million on the enrolment of the first patient in a Phase 3 FDA trial for a second skin indication
4. US$8.0 million on FDA approval of a prescription product for a skin indication
5. US$8.0 million on FDA approval of a prescription product for a second skin indication

The purchase price for Santalis will increase by a maximum of US$20.0 million if the following milestones are achieved in the five years after completion:
1. US$5.0 million on the launch of a new OTC product
2. US$2.5 million on the enrolment of the first patient in a Phase 3 FDA trial for a skin indication
3. US$2.5 million on the enrolment of the first patient in a Phase 3 FDA trial for a second skin indication 4. US$5.0 million on FDA approval of a prescription product for a skin indication
5. US$5.0 million on FDA approval of a prescription product for a second skin indication
If FDA approval of a prescription product (milestones 4 and 5 above) is granted between five and eight years post completion, then 50% of the relevant milestone payment will be payable.

All milestone payments are payable in stock and/ or cash, at TFS’s election and in such proportions as TFS determines.
Base earn out payments
The purchase price for ViroXis will increase by a maximum of US$50.0 million based on the level of aggregate net cash flow ("NCF") generated by the business in the five years post completion. The base earn out payment thresholds are:
No earn out payment Less than US$4.3 million US$5.0 million NCF equal to or greater than US$4.3 million and less than US$8.6 million US$15.0 million NCF equal to or greater than US$8.6 million and less than US$12.8 million US$35.0 million NCF equal to or greater than US$12.8 million and less than US$17.1 million US$50.0 million NCF equal to or greater than US$17.1 million

The purchase price for Santalis will increase by a maximum of US$31.0 million based on the level of aggregate net cash flow ("NCF") generated by the business in the five years post completion. The base earn out payment thresholds are:
No earn out payment Less than US$2.5 million US$5.0 million NCF equal to or greater than US$2.5 million and less than US$5.0 million US$10.0 million NCF equal to or greater than US$5.0 million and less than US$7.4 million US$20.0 million NCF equal to or greater than US$7.4 million and less than US$9.9 million US$31.0 million NCF equal to or greater than US$9.9 million

All base earn out payments are payable in stock and/ or cash, at TFS’s election and in such proportions as TFS determines.

Incentive earn out payments
The purchase price for ViroXis will increase by an incentive earn out payment equal to 20% of the NCF in excess of US$10.0 million for each of the three years ending on the six, seven and eight year anniversaries of completion. The incentive earn out payment is capped at US$60.7 million.

The purchase price for Santalis will increase by an incentive earn out payment equal to 20% of the NCF in excess of US$10.0 million for each of the three years ending on the six, seven and eight year anniversaries of completion. The incentive earn out payment is capped at US$37.5 million.

All incentive earn out payments are payable in stock and/ or cash, at TFS’s election and in such proportions as TFS determines.
Final earn out payments
The purchase price for ViroXis will increase by a final earn out payment equal to 20% of the amount, if any, that aggregate NCF for the 8 year period after completion exceeds US$111.9 million, subject to the maximum purchase price cap for all purchase payments of US$154.9 million.
The purchase price for Santalis will increase by a final earn out payment equal to 20% of the amount, if any, that aggregate NCF for the 8 year period after completion exceeds US$111.7 million, subject to the maximum purchase price cap for all payments of US$90.0 million.
All final payments are payable in stock or cash, at TFS’s election and in such proportions as TFS determines.

Put and call mechanism: Santalis In accordance with the terms of the Santalis share purchase agreement, Mr Clements and Dr Castella will initially retain some of their Santalis shares following completion of the Acquisitions (which is expected to be in July 2015).

There are put and call options in place between TFS and Mr Clements and Dr Castella which are exercisable prior to 31 July 2016. These options require TFS to acquire the retained shares on the same terms as TFS acquired the balance of the shares at completion and TFS expects to exercise its call option within this timeframe.

Additional requirements
Further to the purchase prices, TFS will provide minimum funding support to ViroXis and Santalis for product development and other costs. The costs to TFS will be US$2.5 million per year for five years for each of ViroXis and Santalis (total of US$25 million over 5 years).

On June 18, 2015 TG Therapeutics reported updated clinical results from its Phase 2 study of TG-1101 (ublituximab), the Company’s novel glycoengineered anti-CD20 monoclonal antibody, in combination with ibrutinib, the oral BTK inhibitor (Filing, 8-K, TG Therapeutics, JUN 18, 2015, View Source [SID:1234505460]). The updated results from the Phase 2 study were delivered in an oral presentation by Dr. John Burke, Rocky Mountain Cancer Associates/US Oncology, Aurora, CO during the 13th International Congress on Malignant Lymphoma (ICML), being held from June 17 – June 20, 2015 in Lugano, Switzerland.

OVERVIEW OF THE UPDATED RESULTS PRESENTED ON TG-1101 + IBRUTINIB

Today’s presentation included data from 44 patients with relapsed and/or refractory CLL treated with TG-1101 in combination with ibrutinib at the labeled dose of 420 mg. Forty patients were evaluable for efficacy, of which 50% (20 patients) were considered "High-Risk", defined as the presence of a 17p del, 11q del and/or p53 mutation, the same criteria which is being used for the current Phase 3 GENUINE study.

Dr. Jeff Sharman, Medical Director of Hematology Research for the US Oncology Network, and Study Chair for both the Phase 2 and the Phase 3 GENUINE Study stated: "The updated Phase 2 data continues to demonstrate that adding ublituximab to ibrutinib can induce not only significant response rates for high-risk CLL patients, but has the potential to impact depth of response, with higher CR and MRD negative rates observed compared to historical data with ibrutinib monotherapy. The Phase 3 study is now up and running, and we look forward to a strong collaboration with all investigators, as this is a very attractive protocol for patients with high-risk CLL."

Michael S. Weiss, the Company’s Executive Chairman and Interim CEO commented on the data, "We continue to be pleased with the performance of the combination of TG-1101 plus ibrutinib and continue to believe the combination represents a best-in-class treatment for patients with relapsed/refractory CLL, especially in patients with high-risk disease, which is generally known to be chemotherapy resistant. We expect, if approved, TG-1101 will be the first chemo-free combination approved with ibrutinib for patients with relapsed/refractory CLL. The data presented today gives us additional confidence that the outcome of our Phase 3 GENUINE Study will be successful and we will be able to offer patients a novel chemo-free treatment option. We greatly appreciate the dedication to the program from our Study Chair Dr. Jeff Sharman and all the participating sites and physicians across the country that are participating in this important clinical trial."

Safety and Tolerability of TG-1101 + ibrutinib

TG-1101 in combination with ibrutinib was well tolerated in the 44 CLL patients evaluable for safety, with day 1 infusion related reactions (IRR) being the most frequently reported adverse event (regardless of causality), the majority of which were Grade 1 or 2 in severity. Only 3 Grade 3 or 4 adverse events were observed in > 5% of patients: neutropenia (11%), anemia (11%), and IRR (7%). Adverse events were manageable with only 7% of CLL patients (3/44) discontinuing from the study due to an adverse event: 1 diarrhea (attributed to ibrutinib) and 2 non-related adverse events. Overall, aside from day 1 IRR, the addition of TG-1101 to ibrutinib did not appear to alter the safety and tolerability profile of ibrutinib monotherapy.

Clinical Activity of TG-1101 + ibrutinib

Of the 44 CLL patients treated, 40 were evaluable for response. The 4 patients who were not evaluable included 2 who discontinued due to an adverse event and 2 who withdrew consent, in each case, prior to a first efficacy assessment. Of the 20 CLL patients with previously treated high-risk disease, the patient population we are currently studying in our Phase 3 GENUINE study, 95% (19/20) achieved an objective response with 20% achieving MRD negativity and/or a CR or an unconfirmed CR (pending bone marrow confirmation) as per the iwCLL (Hallek 2008). Additionally, disease response improved for the high-risk CLL patients from a median 64% nodal reduction by month 3 to a median 85% nodal reduction by month 6.

Amongst all 40 CLL patients evaluable for efficacy, 88% (35/40) achieved an objective response per the iwCLL (Hallek 2008) criteria and 4 patients, or an additional 10%, achieved nodal reductions ranging from 20%-55%, without disease progression.

TG-1101 also appeared to abrogate ibrutinib related lymphocytosis with patients experiencing a median 75% reduction in their absolute lymphocyte count (ALC) by the end of month 3 following initiation of combination therapy and 70% of patients achieving normal ALC ranges (< 4,000/uL) by month 6.

ADDITIONAL ICML MEETING PRESENTATIONS

In addition to the TG-1101 + ibrutinib data, the following data, which was presented previously at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper), was presented at the 13th International Congress on Malignant Lymphoma (ICML) meeting:

· Single agent TGR-1202 in patients with relapsed or refractory CLL, NHL or other B-cell Malignancies: Oral Presentation (Owen A. O’Connor, MD, PhD)
· Combination of TG-1101 + TGR-1202 (the Company’s "1303" combination) in patients with relapsed/refractory NHL and high-risk CLL: Poster Presentation (Matt Lunning, DO)
· Chemo-free triplet combination of TG-1101 + TGR-1202 + ibrutinib in patients with B-cell malignancies: Oral Presentation (Loretta Nastoupil, MD)

A copy of all data presentations from the ICML Lugano meeting can be found at View Source

ABOUT THE GENUINE PHASE 3 TRIAL (TG-1101 + IBRUTINIB)

The Phase 3 trial, the "GENUINE" trial, evaluating TG-1101 (ublituximab) in combination with ibrutinib compared to ibrutinib alone for the treatment of patients with previously treated high-risk CLL is now open in over 120 centers across the US and is actively enrolling patients. The trial is being conducted under Special Protocol Assessment (SPA) which provides agreement that the Phase 3 trial design adequately addresses objectives that would support the regulatory submission for drug approval.

The GENUINE trial will enroll approximately 330 patients, with approximately the first two-thirds of the patients included in the ORR assessment. As per the SPA, the Company plans to use the ORR data from the trial as the basis for submission of a Biologics License Application (BLA) for accelerated approval for TG-1101. All patients will then be followed for progression free survival (PFS) assessment, which is designed to support full approval.

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