On July 10, 2019 Transgene (Paris:TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of solid tumors, reported it has received the approval from the UK Medicines and Healthcare Products Regulatory Agency (MHRA) to proceed with a Phase 1 clinical trial of its lead myvacTM candidate TG4050 (Press release, Transgene, JUL 10, 2019, View Source [SID1234537466]). TG4050 is being developed as a potential treatment for patients with newly diagnosed, locoregionally advanced, HPV negative, squamous cell carcinoma of the head and neck (SCCHN).

TG4050 is an individualized MVA-based immunotherapy derived from the myvacTM platform. It has been designed to stimulate and educate the patient’s immune system to recognize and destroy tumor cells. Tumor cells accumulate mutations and each patient has a set of mutations that are unique to their tumor. TG4050 has been designed to target a panel of these patient specific mutations, which have been selected using NEC’s Neoantigen Prediction System.

"This trial builds upon a long-term research collaboration in the field of immunology of cancer between Transgene and the University of Southampton. It will allow us to bring a very innovative individualized approach to patients. I expect the study to provide us with data demonstrating the safety and immunogenicity of TG4050. I believe such personalized vaccine approaches are the next paradigm in cancer care and could redefine the way patients with H&N cancer and other solid tumors will be treated" said lead investigator Pr. Christian Ottensmeier, MD, PhD, FRCP, Professor of Experimental Medicine within Medicine at the University of Southampton.

The Phase 1 clinical trial of TG4050 will be carried out in patients with SCCHN that have received an adjuvant (first line) therapy. Antitumor activity of TG4050 as monotherapy will also be measured. This multi-center, open label, two arms trial will include patients in the UK and in France.

The study, sponsored by Transgene, will be co-financed by Transgene and its partner NEC, which will also support the trial by contributing to the therapeutic vaccine design and the selection of target neoantigens (see press release dated March 5, 2019).

Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene commented, "This approval from MHRA follows our recent IND from the FDA in ovarian cancer, allowing us to conduct Phase 1 clinical trials with TG4050 in both the US and Europe. With our partner NEC, we look forward to updating you on the progress on both of these clinical trials. These studies will also provide us with important insights into the optimal way to manufacture this novel individualized immunotherapy which is made specifically for each cancer patient."

TG4050 has also been granted an IND from the US FDA to evaluate TG4050 as a potential treatment for ovarian cancer patients (see press release dated May 13, 2019).

About TG4050
TG4050 is an immunotherapy designed to stimulate the immune system of patients in order to induce a response that is able to recognize and destroy tumor cells in a specific manner.
This personalized immunotherapy is developed for each patient, on the basis of mutations identified through sequencing of tumor tissue, prioritized using NEC’s Neoantigen Prediction System and delivered using the myvacTM technological platform which allows development and manufacture of a product that is specific to each patient and that is within time frames compatible with clinical management.

About myvacTM
myvacTM is a viral vector (MVA) based, individualized immunotherapy platform that has been developed by Transgene to target solid tumors. myvacTM-derived products are designed to stimulate the patient’s immune system, recognize and destroy tumors using the patient’s own cancer specific genetic mutations. Transgene has set up an innovative network that combines bioengineering, digital transformation, established vectorization know-how and unique manufacturing capabilities. Transgene has been awarded an "Investments for the Future" funding from Bpifrance for the development of its platform myvacTM.

About NEC’s Neoantigen Prediction System
NEC’s neoantigen prediction utilizes its proprietary artificial intelligence (AI), such as graph-based relational learning, which is combined with other sources of data to discover candidate neoantigen targets. NEC comprehensively evaluates the candidate neoantigens with a primary focus placed on its in-house MHC-binding affinity prediction. These allow NEC to effectively prioritize the numerous candidate neoantigens identified in a single patient.

On July 10, 2019 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the company has signed a definitive agreement under which Jazz has acquired Redx Pharma’s (Redx) pan-RAF inhibitor program for the potential treatment of RAF and RAS mutant tumors (Press release, Jazz Pharmaceuticals, JUL 10, 2019, View Source [SID1234537445]). Redx will perform certain pre-clinical activities for the program under a separate collaboration agreement with Jazz. Jazz will be responsible for further development, regulatory activities and commercialization.

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Under the terms of the agreement, Jazz will pay Redx an upfront payment of $3.5 million. Redx is eligible to receive up to $203 million in development, regulatory and commercial milestone payments from Jazz, and incremental tiered royalties in mid-single digit percentage, based on any future net sales.

"We are excited to acquire Redx’s pan-RAF inhibitor program. It has the potential to work in RAF driven tumors where current selective B-RAF inhibitors and their respective combinations are ineffective due to acquired resistance mechanisms. In addition, there is the potential to address RAS driven tumors," said Robert Iannone, M.D., M.S.C.E., executive vice president, research and development of Jazz Pharmaceuticals. "We look forward to advancing the pan-RAF inhibitor program that is part of a novel class of next generation precision oncology drugs and is highly complementary to our growing R&D portfolio of early-stage, innovative, hematology/oncology therapies."

About Pan-RAF Inhibitors1,2,3
Mutations leading to uncontrolled signalling via the RAS-RAF-MAPK pathway are seen in more than one third of all cancers. The pan-RAF inhibitor program aims to overcome resistance mechanisms associated with clinically approved B-RAF selective drugs.

The RAF kinases (A-RAF, B-RAF and C-RAF) are an integral part of this pathway, with B-RAF mutations commonly seen in the clinic. Although most B-RAF V600E mutant skin cancers are sensitive to approved B-RAF selective drugs, B-RAF V600E mutant colorectal cancers are surprisingly insensitive to these agents as monotherapy due to the functions of other RAF family members and require combination therapy.

B-RAF selective therapies fail to show clinical benefit against atypical B-RAF (non-V600E), other RAF and RAS driven tumors. Pre-clinical study results of Redx’s pan-RAF program have demonstrated in vivo efficacy in a B-RAFV600E mutant colorectal cancer xenograft model as a single agent, where approved B-RAF selective drugs are ineffective as monotherapy. It has also shown promising activity in RAS-mutated cancer cells.

On July 10, 2019 AngioDynamics, Inc. (NASDAQ: ANGO), a leading provider of innovative, minimally invasive medical devices for vascular access, peripheral vascular disease, and oncology, reported financial results for the fourth quarter of fiscal year 2019, which ended May 31, 2019 (Press release, AngioDynamics, JUL 10, 2019, View Source [SID1234537467]).

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"Fiscal year 2019 was an exciting and transformative year for AngioDynamics. I am very pleased with our fourth quarter and full-year performance, as we achieved solid revenue growth and continued to implement meaningful operational improvements," commented Jim Clemmer, President and Chief Executive Officer of AngioDynamics, Inc. "During the quarter, we strengthened our balance sheet and made significant progress towards our long-term portfolio management goals through the sale of our NAMIC Fluid Management business, setting us on a path towards becoming a leaner, more innovation-focused company. We also made significant strides with our NanoKnife platform, enrolling the first patient in our DIRECT study for pancreatic cancer and receiving FDA approval to initiate a pilot study for the treatment of prostate cancer. I am extremely proud of all of the members of our AngioDynamics team for their hard work during the year, and I look forward to sustaining and growing this momentum throughout fiscal year 2020."

Fourth Quarter 2019 Financial Results

Net sales for the fourth quarter of fiscal 2019 were $96.3 million, an increase of 9.0%, compared to $88.3 million a year ago. Foreign currency translation did not have a significant impact on the Company’s sales in the quarter.

Oncology net sales were $15.3 million, an increase of 26.5% from $12.1 million a year ago. Strong sales of Solero, along with the recent BioSentry and RadiaDyne acquisitions, more than offset lower NanoKnife capital sales during the quarter.
Vascular Interventions and Therapies net sales were $56.2 million, an increase of 6.9%, compared to $52.6 million a year ago, as strong growth in AngioVac and our Core product line offerings was partially offset by a decline in the Venous Insufficiency business.
Vascular Access net sales were $24.8 million, an increase of 4.9% from $23.7 million a year ago, driven by higher sales of midlines, ports and dialysis.
U.S. net sales in the fourth quarter of fiscal 2019 were $73.4 million, an increase of 4.4% from $70.3 million a year ago, and International net sales were $22.9 million, an increase of 27.0% from $18.0 million a year ago.

Gross margin for the fourth quarter of fiscal 2019 was 53.6%, roughly flat compared to the year ago quarter as improvements in net productivity and higher volume were offset by negative impacts of price and product mix.

The Company recorded net income of $58.9 million, or $1.54 per share, in the fourth quarter of fiscal 2019. This compares to net income of approximately $2.1 million, or $0.06 per share, a year ago. Net income was favorably impacted in the fourth quarter of fiscal 2019 by the gain on the sale of the NAMIC fluid management business of $46.6 million.

Excluding the items shown in the non-GAAP reconciliation table below, adjusted net income for the fourth quarter of fiscal 2019 was $9.6 million, or $0.25 per share, compared to adjusted net income of $7.7 million, or $0.20 per share, in the fourth quarter of fiscal 2018.

Adjusted EBITDAS in the fourth quarter of fiscal 2019, excluding the items shown in the reconciliation table below, was $17.6 million, compared to $15.6 million in the fourth quarter of fiscal 2018.

In the fourth quarter of fiscal 2019, the Company generated $25.0 million in operating cash flow and had capital expenditures of $0.9 million. As of May 31, 2019, the Company had $227.6 million in cash and cash equivalents and $132.5 million in debt, excluding the impact of deferred financing costs.

Full-Year 2019 Financial Results

For the twelve months ended May 31, 2019:

Net sales were $359.5 million, an increase of 4.4%, compared to $344.3 million for the same period a year ago.
The Company’s net income was $61.3 million, or $1.61 per share, compared to net income of $16.3 million, or $0.44 per share, a year ago.
Gross margin improved 200 basis points to 53.4% from 51.4% a year ago.
Excluding the items shown in the non-GAAP reconciliation table below, adjusted net income was $31.6 million, or $0.83 per share, compared to adjusted net income of $27.6 million, or $0.74 per share, a year ago.
Adjusted EBITDAS, excluding the items shown in the reconciliation table below, was $61.5 million, compared to $57.0 million for the same period a year ago.
Pro Forma 2019 Performance

In addition to actual results, the tables accompanying this press release reflect pro forma results, which exclude the full-year impact of the NAMIC Fluid Management business that was divested on May 31, 2019.

Fiscal Year 2020 Financial Guidance

The Company expects its fiscal year 2020 net sales to be in the range of $280 to $286 million and adjusted earnings per share in the range of $0.25 to $0.30. Additionally, the Company expects gross margin to be in the range of 58% to 59%.

Conference Call

The Company’s management will host a conference call today at 8:00 a.m. ET to discuss its fiscal fourth quarter and full-year 2019 results.

To participate in the conference call, dial 1-877-407-0784 (domestic) or 1-201-689-8560 (international) and refer to the passcode 13691777.

This conference call will also be webcast and can be accessed from the "Investors" section of the AngioDynamics website at www.angiodynamics.com. The webcast replay of the call will be available at the same site approximately one hour after the end of the call.

A recording of the call will also be available from 11:00 a.m. ET on Wednesday, July 10, 2019, until 11:59 p.m. ET on Wednesday, July 17, 2019. To hear this recording, dial 1-844-512-2921 (domestic) or 1-412-317-6671 (international) and enter the passcode 13691777.

Use of Non-GAAP Measures

Management uses non-GAAP measures to establish operational goals and believes that non-GAAP measures may assist investors in analyzing the underlying trends in AngioDynamics’ business over time. Investors should consider these non-GAAP measures in addition to, not as a substitute for or as superior to, financial reporting measures prepared in accordance with GAAP. In this news release, AngioDynamics has reported adjusted EBITDAS, adjusted net income, adjusted earnings per share and free cash flow. Management uses these measures in its internal analysis and review of operational performance. Management believes that these measures provide investors with useful information in comparing AngioDynamics’ performance over different periods. By using these non-GAAP measures, management believes that investors get a better picture of the performance of AngioDynamics’ underlying business. Management encourages investors to review AngioDynamics’ financial results prepared in accordance with GAAP to understand AngioDynamics’ performance taking into account all relevant factors, including those that may only occur from time to time but have a material impact on AngioDynamics’ financial results. Please see the tables that follow for a reconciliation of non-GAAP measures to measures prepared in accordance with GAAP.

On July 10, 2019, Forty Seven reported that entered into an exclusive license and collaboration agreement with Ono Pharmaceutical Co., Ltd., or Ono (Filing, 8-K, Forty Seven, JUL 10, 2019, View Source [SID1234537499]). Under the agreement, we granted Ono an exclusive license to develop, manufacture and commercialize 5F9, our monoclonal antibody against CD47, as well as other anti-CD47 antibodies controlled by us in Japan, South Korea, Taiwan and the ASEAN countries, or the Ono Territory. We retain all rights to 5F9 and other licensed antibodies outside of the Ono Territory.

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Under the agreement, the parties will collaborate on the development, manufacturing and commercialization of 5F9 and other licensed antibodies. Each party will be responsible for conducting development and commercialization of licensed antibodies in its respective territory at its own cost. Further, each party will have the right to participate, at its cost, in global clinical studies of 5F9 and other licensed antibodies conducted by the other party. We will initially be responsible for supplying 5F9 and other licensed antibodies to Ono for development and commercialization within the Ono Territory at Ono’s cost. Ono has the right to elect that such manufacturing activities be transferred to Ono. During the term of the agreement, neither party may manufacture or commercialize any competing products in the Ono Territory.

We will receive a one-time upfront payment of approximately $15.8 million from Ono and will be eligible to receive up to an additional approximately $104 million at current exchange rates if specified future development and commercial milestones are achieved by Ono. We are also eligible to receive tiered percentage royalties spanning from the mid-teens to the low-twenties on future net sales of 5F9 and other licensed antibodies in the Ono Territory, subject to certain offsets. Ono’s obligation to pay royalties expires, on a product-by-product and country-by-country basis, on the later of (1) the expiration of the first regulatory exclusivity for such product in such country, (2) the expiration of the last to expire patent controlled by us that covers the composition of matter of a licensed antibody in such product in such country, or (3) the tenth anniversary of the first commercial sale of such product in such country.

The agreement will remain in effect until the expiration of all of Ono’s royalty obligations, after which Ono’s license shall be fully paid-up. Ono may terminate the agreement on a country-by-country basis for convenience upon 90 days’ prior written notice to us prior to the first commercial sale of the first licensed product in the Ono Territory, or 180 days’ prior written notice after such first sale. Either party may also terminate the agreement for the other party’s uncured material breach or insolvency, subject to specified notice and cure periods. In the event of any early termination, all rights in 5F9 and other licensed antibodies will revert to us, subject to certain royalties due to Ono in the case of Ono’s termination for our breach or insolvency.

This summary is qualified in its entirety by reference to the text of the exclusive license and collaboration agreement which we intend to file as an exhibit to our Quarterly Report on Form 10-Q for the quarter ending September 30, 2019.

On July 10, 2019 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, and I-Mab Biopharma (I-Mab), a China and U.S.-based clinical-stage biopharmaceutical company committed to the discovery and development of first-in-class and best-in-class biologics in immuno-oncology and autoimmune diseases, reported that the companies have entered into an exclusive collaboration and license agreement to develop and commercialize enoblituzumab (Press release, MacroGenics, JUL 10, 2019, View Source [SID1234537468]). This investigational drug is an immune-optimized, anti-B7-H3 monoclonal antibody that incorporates MacroGenics’ proprietary Fc Optimization technology platform. Enoblituzumab represents one of the most advanced programs in development directed against B7-H3, a target for which no agent is currently approved. I-Mab obtains regional development and commercialization rights in mainland China, Hong Kong, Macau and Taiwan.

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As part of the collaboration, I-Mab will both lead regional studies in its territories as well as participate in global studies conducted by MacroGenics. MacroGenics intends to initiate a Phase 2 study of enoblituzumab in combination with MGA012 (also known as INCMGA0012), an investigational anti-PD-1 antibody that MacroGenics licensed to Incyte Corporation, in first-line patients with head and neck cancer later this year.

"We are very pleased to be partnering with I-Mab to further accelerate and broaden the development of enoblituzumab and to support our mission of bringing innovative medicines to patients with high unmet medical needs," said Scott Koenig, M.D., Ph.D., President and Chief Executive Officer of MacroGenics. "We believe that I-Mab is an ideal partner given its track record of rapidly progressing innovative immuno-oncology programs and its ability to tap into the growing pharmaceutical market in this region."

"MacroGenics is recognized as a leader in the development of therapeutics targeting B7-H3 and we are committed to accelerating the development of enoblituzumab, a promising investigational drug which may represent a new treatment paradigm in immuno-oncology," said Jingwu Zang, M.D., Ph.D., Chief Executive Officer of I-Mab. "We believe that this program is an exciting addition to our innovative pipeline of clinical stage oncology assets."

MacroGenics expects to receive an upfront payment of $15 million in connection with the collaboration. MacroGenics will also be eligible to receive additional development and regulatory milestone payments of up to $135 million. In addition, I-Mab will pay tiered double-digit royalties (ranging from mid teens to twenty percent) based on annual net sales in the territories.

About Enoblituzumab Program

Enoblituzumab is an investigational Fc-optimized monoclonal antibody that targets B7-H3, a member of the B7 family of immune regulator proteins. B7-H3 is widely expressed by a number of different tumor types and may play a key role in regulating the immune response to various types of cancer. Encouraging data from the Phase 1 clinical study of enoblituzumab in combination with an anti-PD-1 antibody were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in November 2018. Based on these data, MacroGenics is planning to initiate a Phase 2 study of enoblituzumab in combination with MGA012 in patients with squamous cell carcinoma of the head and neck (SCCHN) in the second half of 2019.

About MacroGenics’ Fc-Optimization Technology

MacroGenics’ Fc-Optimization platform is designed to modulate an antibody’s interaction with immune effector cells. The Fc region of certain antibodies binds activating and inhibitory receptors, referred to as FcγRs, on immune cells found within the innate immune system. Such interactions affect killing of cancer cells through antibody dependent cellular cytotoxicity (ADCC), among other Fc-dependent functions.

MacroGenics’ optimized Fc region binds with increased affinity to the activating CD16A FcγR and unique to MacroGenics’ technology, with reduced affinity to CD32B, the inhibitory FcγR. MacroGenics’ optimized Fc mediates improved effector functions, such as ADCC. To date, MacroGenics has successfully incorporated its proprietary Fc Optimization technology in enoblituzumab, as well as margetuximab, an investigational anti-HER2 monoclonal antibody currently in Phase 3 development.