AVEO Oncology Announces Receipt of Payments from EUSA Pharma and CANbridge

On September 13, 2017 AVEO Oncology (NASDAQ:AVEO) reported the receipt of a $4 million research and development payment from EUSA Pharma related to the approval of FOTIVDA (tivozanib) for the treatment of adult patients with advanced renal cell carcinoma in Europe, and a $0.5 million milestone payment from CANbridge related to manufacturing development activities for AV-203, AVEO’s clinical-stage ErbB3 (HER3) inhibitory antibody candidate (Press release, AVEO, SEP 13, 2017, View Source;p=RssLanding&cat=news&id=2300267 [SID1234520501]).

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"These payments further strengthen our balance sheet while demonstrating the value of our partnerships in advancing AVEO’s pipeline," said Michael Bailey, president and chief executive officer of AVEO. "Additionally, these payments add to our current cash on hand, which was expected to fund operations into the fourth quarter of 2018. We look forward to several additional key milestones in the coming quarters, including the expected presentation of tivozanib-nivolumab combination Phase 1 TiNivo study results this fall, and the anticipated readout of our pivotal Phase 3 TIVO-3 trial in the first quarter of 2018."

Under the terms of their December 2015 agreement, EUSA Pharma has agreed to pay AVEO up to $390 million in future milestone payments and research and development funding, assuming successful achievement of specified development, regulatory and commercialization objectives. In addition, a tiered royalty will be due to AVEO ranging from a low double-digit up to mid-twenty percent on net sales of tivozanib in the agreement’s territories. With European approval, AVEO will be eligible for up to $12 million in milestones from EUSA based on reimbursement and regulatory approvals. In the territories licensed to EUSA, thirty percent of milestone and royalty payments received by AVEO, excluding research and development payments such as the one announced today, are due to Kyowa Hakko Kirin (KHK) as a sublicensing fee. In the territories retained by AVEO, the royalty obligation to KHK ranges from the low- to mid-teens on net sales.

In March 2016, AVEO announced an exclusive collaboration and license agreement, granting CANbridge worldwide rights to AV-203, excluding the United States, Canada, and Mexico. Under the terms of the collaboration and license agreement, AVEO is eligible to receive up to $132 million in future reimbursement and milestone payments, assuming the successful achievement of specified development, regulatory and commercialization objectives, as well as a tiered royalty, with a percentage range in the low double digits, on net sales of AV-203 in the partnered territories.

AVEO has retained North American rights to tivozanib and AV-203.

Transgene: First Half-Year 2017 in Line with Our Objectives: All Clinical Programs Progressing and New Collaboration Agreements Signed

On September 13, 2017 Transgene (Paris:TNG), a biotechnology company focused on designing and developing viral-based immune-targeted therapies, reported its financial results for the six-month period ended June 30, 2017, and reviews the progress of it products portfolio since the beginning of the year (Press release, Transgene, SEP 13, 2017, View Source [SID1234520500]).

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Philippe Archinard, Chairman and Chief Executive Officer of Transgene said: "Transgene is continuing to successfully execute its strategy. We are making progress with our clinical development plans with seven active trials as of today, and in parallel we are continuing to advance our cutting edge research program.

Four of the clinical trials are aiming to confirm the potential of TG4010 or Pexa-Vec in combination with immune checkpoint inhibitors (ICIs), including in two high unmet need indications, lung and liver cancer.

We have signed two collaborations, one with Bristol-Myers Squibb (BMS) covering a combination study with TG4010 in the first-line treatment of lung cancer, and one with Servier for the design of an optimized production process of allogenic CAR-T cells using our viral vectorization technology. These new deals build on our existing collaborations with BMS for TG4010 in the 2nd-line treatment of lung cancer and with Merck KGaA/Pfizer for TG4001 in head and neck cancers. We believe these agreements provide strong validation of the potential of our immunotherapy approach.

With our current funding, Transgene is well placed to progress its programs through to the end of 2018. We will continue to focus all of our energy to advance our multiple clinical trials and to seize the development opportunities that they could create for Transgene."

Product pipeline review

1. Therapeutic Vaccines

TG4010: combination trial with nivolumab (ICI); collaborations with Bristol-Myers Squibb

TG4010 is a therapeutic vaccine being developed in advanced-stage non-squamous non-small cell lung cancer (NSCLC). TG4010’s mechanism of action, excellent safety profile and existing clinical data make it a very suitable candidate for combinations with other therapies.

The clinical trials aim to confirm the synergies that are expected to result from the combination of a therapeutic vaccine and an ICI. The expected clinical benefits of the combination are an increase in the response rate, in the quality and in the duration of the response to current and future standards of care.

TG4010
+ Opdivo (ICI)
(nivolumab)
+ chemotherapy
Phase 2

Non-small cell lung cancer (NSCLC) – 1st-line

Collaboration deal signed in April 2017 with Bristol-Myers Squibb, that will supply nivolumab
Preparation of a Phase 2 clinical trial combining TG4010 with nivolumab and with chemotherapy in patients with tumor cells expressing low or undetectable levels of PD-L1
FDA IND approval granted to begin the clinical trial in the USA
First patient expected to be enrolled at the end of 2017
TG4010
+ Opdivo (ICI)
(nivolumab)
Phase 2
Non-small cell lung cancer (NSCLC) – 2nd-line

Trial of TG4010 in combination with nivolumab, that will be provided by Bristol-Myers Squibb, within a collaborative agreement with UC Davis Medical Center (USA) – Principal investigator: Dr. Karen Kelly
First patient treated in March 2017; the trial’s 4 sites are now open
First results expected beginning of 2018
TG4001: trial in combination with avelumab (ICI), based on a collaboration agreement with Merck KGaA and Pfizer

TG4001 is a therapeutic vaccine that has already been administered to more than 300 subjects in previous clinical trials. TG4001 has demonstrated good tolerability, a significant HPV clearance rate and promising efficacy results. Its mechanism of action and good safety profile make TG4001 an appropriate candidate for combinations with other therapies.

TG4001
+ Bavencio (ICI)
(avelumab)
Phase 1/2

HPV positive head and neck cancer – 2nd-line

Clinical collaboration agreement with Merck KGaA and Pfizer, for the supply of avelumab for the trial
Principal investigator: Prof. Christophe Le Tourneau (Institut Curie, Paris); multi-center trial
First patient expected to be treated shortly
TG1050: results expected in 2H 2017

TG1050 is a therapeutic vaccine for the treatment of chronic hepatitis B. At the end of 2015, Transgene started a study evaluating the safety and tolerability of TG1050 in patients who are currently being treated for chronic HBV infection with standard-of-care antiviral therapy. The technology of TG1050 is also being developed in China, where Transgene operates a joint-venture with Tasly Biopharmaceutical Technology.

TG1050
+ Standard-of-
Care Antiviral
Phase 1/1b

Chronic hepatitis B

Results from the first part of the study to be presented at AASLD (October 2017)
Several patents granted, extending protection to 2032
2. Oncolytic viruses

Pexa-Vec: ongoing Phase 3 trial, initiation of the Phase 2 clinical combination trials

Pexa-Vec is an oncolytic virus designed to selectively target and destroy cancer cells through intracellular viral replication (oncolysis), and by stimulating the body’s immune response against cancer cells. Its mechanism of action and tolerability profile make it an appropriate candidate for use in combinations.

Pexa-Vec
+ sorafenib
(PHOCUS)
Phase 3

Advanced liver cancer (hepatocellular carcinoma – HCC) – 1st-line

Clinical trial being conducted by SillaJen, Inc., Transgene’s partner
Ongoing recruitment. First patient treated in Europe in April 2017
Trial recruitment authorized in China (July 2017)
First data readout expected in 2019
Pexa-Vec
+ Opdivo (ICI)
(nivolumab)
Phase 2
Advanced liver cancer (hepatocellular carcinoma – HCC) – 1st-line

Principal investigator: Prof. Olivier Rosmorduc (Pitié Salpêtrière, Paris)
First patient treated in July 2017; several active trial sites
First data readout expected in 2018
Pexa-Vec
+ metronomic
cyclophosphamide
Phase 1/2
HER2 negative breast cancer et soft tissue sarcoma (METROmaJX)

Principal investigator: Prof. Antoine Italiano (Institut Bergonié, Bordeaux); Sponsor : INCa
Positive results of the Phase 1 part presented at ESMO (Free ESMO Whitepaper) 2017 (Sept. 2017)
First patient of the Phase 2a part treated in April 2017
Pexa-Vec
+ Yervoy (ICI)
(ipilimumab)
Phase 1
Solid tumors (ISI-JX)

Principal investigator: Dr. Aurélien Marabelle, MD, PhD (Centre Léon Bérard, Lyon)
First patient treated in February 2017
First readout expected around the end of 2017
TG6002: preparation of first-in-human trial

TG6002 is a next generation oncolytic immunotherapy. It has been designed to induce the breakdown of cancer cells (oncolysis) and express the FCU1 gene in the cancer cells it has infected leading to the local production of 5-FU, a widely-used chemotherapy. TG6002 could potentially be used both in combination or as monotherapy in recurrent cancers.

TG6002
Phase 1

Glioblastoma

Principal investigator: Prof. J-Y Delattre (AP-HP, Paris), with the support of INCa (French national cancer institute)
First patient expected in the coming weeks
3. Research and preclinical portfolio

Research and preclinical highlights during the first half were:

The signing of a collaboration agreement with Servier in June 2017 aimed at designing an original process for the production of allogenenic CAR-T cells which would provide better yield and a reduced number of steps. This collaboration highlights Transgene’s expertise in viral vectorization;
A poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) meeting in April 2017 and the publication of preclinical data supporting the clinical development of TG6002 in Cancer Research in July 2017;
The filing of several patent applications ensuring the protection of the innovative technologies developed by Transgene for new products (therapeutic vaccines and oncolytic viruses).
A R & D Day for investors on 22 June 2017 in Paris. At this meeting, Transgene presented its new generation of immunotherapies based on multifunctional (armed) oncolytic viruses aimed at improving the treatment of cancer.
Key financials

The Board of Directors of Transgene met on September 12, 2017, and reviewed the financial statements for the six-month period ended June 30, 2017. The Statutory Auditors have conducted a review of the interim consolidated financial statements. The half-year financial report is available on Transgene’s website, View Source

Key elements of the income statement

(in thousands of euros) June 30, 2017 June 30, 2016
Operating revenues 3,898 5,339
Research and development expenses (16,855) (12,504)
General and administrative expenses (3,066) (3,406)
Other revenue and (expenses), net (107) (128)
Operating expenses (20,028) (16,038)
Operating income / (loss) (16,130) (10,699)
Net income / (loss) (18,346) (11,639)
Net income / (loss) from discontinued operations - (514)
Comprehensive net income (18,346) (12,153)
Operating revenues amounted to €3.9 million for the first six months of 2017 compared to €5.3 million for the same period in 2016. Excluding the €1.3 million one-off revenue received from Sanofi Chimie in 2016, Transgene’s revenues remained stable compared to the first half of 2016.

Revenues from collaboration and licensing agreements amounted to €0.5 million for the first six months of 2017 versus €1.9 million in the same period in 2016, that included €1.3 million from Sanofi Chimie. Under the collaboration agreement with Servier signed in June 2017, Transgene invoiced an initial amount of €1.0 million. Revenue recognition of this amount will be spread over the initial term of the contract, i.e. 3 years.
Government financing of research expenditures amounted to €3.0 million for the first half of 2017, stable compared to the first half of 2016. These figures included a research tax credit of €3.0 million for the first six months of 2017 compared to €2.9 million for the same period in 2016.
Research and Development (R&D) expenses amounted to €16.9 million for the first half of 2017 compared to €12.5 million for the same period in 2016. This increase was mainly due to the milestone payment of €3.8 million ($4 million) to SillaJen, Inc. triggered by the first patient being recruited in Europe in the Phase 3 trial of Pexa-Vec (Phocus). External expenses for clinical projects also increased by €0.4 million with the development plan progressing notably with our products TG4010, Pexa-Vec and TG1050.

General and administrative expenses decreased to €3.1 million for the first half of 2017 compared to €3.4 million for the same period in 2016.

Net loss amounted to €18.4 million for the first half of 2017 compared to €12.2 million for the same period in 2016.

As of June 30, 2017, the Company’s cash, cash equivalents, available-for-sale financial assets and other financial assets amounted to €43.9 million versus €56.2 million as of December 31, 2016.
Cash burn was €12.3 million for the first half of 2017 compared to €8.2 million for the same period in 2016. This cash burn increase was mainly explained by the milestone payment to Sillajen in H1 2017.

Transgene confirms that it expects 2017 cash burn to be around €30 million, which includes an increase of expenses linked to clinical trials due to the acceleration of the clinical development plan and the milestone payment to SillaJen, Inc.

"Our results for the first six months of 2017 are in line with our expectations. We confirm our financial visibility through to the end of 2018", commented Jean-Philippe Del, Chief Financial Officer of Transgene.

As a reminder, the Company still benefits from access to further additional funding that can be activated in 2017: namely the second tranche of the European Investment Bank (EIB) loan (€10 million).

Actinium Pharmaceuticals Highlights Presence at the Society of Hematologic Oncology 2017 Annual Meeting

On September 13, 2017 Actinium Pharmaceuticals, Inc (NYSE American:ATNM) ("Actinium" or "the Company"), a biopharmaceutical company developing innovative targeted therapies for cancers lacking effective treatment options, reported that the Company will feature two posters highlighting its Actimab-A Phase 2 and Actimab-M Phase 1 clinical trials at the Society of Hematologic Oncology 2017 Annual Meeting (SOHO) (Press release, Actinium Pharmaceuticals, SEP 13, 2017, View Source [SID1234520499]). The posters will be presented as part of the Clinical Trials in Progress section.

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"SOHO is an excellent opportunity to share the potential of our CD33 targeting alpha-particle therapy candidates with the greater hematology community," said Dr. Mark Berger, Actinium’s Chief Medical Officer. "We are excited to demonstrate the capacity of our Alpha Therapy platform to bring trials to the clinic addressing unmet clinical needs."

Actimab-A is enrolling patients in a multicenter Phase 2 trial for patients newly diagnosed with Acute Myeloid Leukemia who are age 60 and above and unfit for standard induction therapy. Actimab-M is a Phase 1 trial that is enrolling patients diagnosed with refractory Multiple Myeloma.

SOHO is expected to draw physicians, researchers, and industry leaders from across the nation and will be held at the Westin Galleria & Oaks in Houston, Texas from September 13th – 16th.

The details of the poster presentations are as follows:

Title: Trial in Progress: A Phase I/II Study of Lintuzumab-Ac225 in Older Patients with Untreated Acute Myeloid Leukemia
Abstract Number: AML-070

Title: Trial in Progress: Phase I Study of Actinium-225 (225Ac)-Lintuzumab in Patients with Refractory Multiple Myeloma
Abstract Number: MM-77

Date: Wednesday, September 13th, 2017
Time: 6:00 – 9:00 PM
Location: Westin Galleria

About Actimab-A

Actimab-A, Actinium’s most advanced alpha-particle candidate, is currently in a 53-patient, multicenter Phase 2 trial for patients newly diagnosed with AML age 60 and above. Actimab-A is being developed as a first-line therapy and is a monotherapy that is administered via two 15-minute injections that are given 7 days apart. Actimab-A targets CD33, a protein abundantly expressed on the surface of AML cells via the monoclonal antibody, HuM195, which carries the potent cytotoxic radioisotope actinium-225 to the AML cancer calls. Actinium-225 gives off high- energy alpha particles as it decays, which kill cancer cells and as actinium-225 decays it produces a series of daughter atoms, each of which gives off its own alpha particle, increasing the chances that the cancer cell will be destroyed. Actimab-A is a second-generation therapy from the Company’s HuM195-Alpha program, which was developed at Memorial Sloan Kettering Cancer Center and has now been studied in almost 90 patients in four clinical trials. Actimab-A has been granted Orphan Drug Designation for newly diagnosed AML age 60 and above.

About Actimab-M

The Actimab-M trial uses a CD33 targeted therapy coupled to actinium 225 (the same agent used in the Actimab-A program), and is in a Phase 1 open label, dose escalation study for patients who have progressing disease after 3 prior multiple myeloma treatment regimens. The Phase 1 trial will estimate maximum tolerated dose (MTD), assess adverse events, measure response rates (objective response rate, complete response rate, stringent complete response rate, very good partial response rate and partial response rate) as well as progression free survival (PFS) and overall survival (OS).

Aurigene, a Wholly Owned Subsidiary Of Dr Reddy’s, And Curis Announce CA-170 Program Update Following Data Presented At ESMO 2017

On September 12th, 2017 Aurigene Discovery reported plans to initiate a Phase 2 trial of CA-170, a PDL1-VISTA inhibitor to be conducted at sites in India (Press release, Aurigene Discovery, SEP 12, 2017, View Source [SID1234624587]). This was announced following the presentation of preliminary data from the initial 34 patients with cancer treated in the dose escalation stage of the Phase 1 trial of CA-170 at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress by Aurigene’s collaborator and licensee of CA-170, Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development and commercialization of innovative and effective therapeutics for the treatment of cancer. The trial has been conducted in the U.S., South Korea and Spain. The Phase 2 trial is the result of the initial safety data and preliminary evidence of clinical benefit observed in the trial.

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CA-170 is an oral small molecule targeting the immune checkpoints PDL1 and VISTA. Data presented at the ESMO (Free ESMO Whitepaper) 2017 conference represent the initial 34 patients treated to date in the dose escalation Phase 1 trial. 30 patients were naïve to prior immunotherapy treatment, while four patients had experienced prior treatment with approved anti-checkpoint antibodies. No dose limiting toxicities were observed at doses ranging from 50 mg to 800 mg once daily dosing examined thus far. CA-170 demonstrated good oral bioavailability and plasma drug levels were shown to increase in a near-linear manner with increasing doses. Evidence of immune modulation, including an increase in activated CD8+ T cells, was observed in patient blood and tumor biopsy samples examined following treatment. Of the 21 patients evaluable for disease assessment, 13 patients experienced disease stabilization. Four immunotherapy treatment-naïve patients treated with CA-170 experienced shrinkage of their tumors. Six patients remained on drug treatment beyond three months, including all four patients with tumor shrinkages. In addition, seven of the 34 patients remain on study and are continuing with treatment.

"These results are consistent with the observations made in the preclinical setting and further affirm CA-170’s mechanism of action as an oral small molecule checkpoint inhibitor. Based on these initial clinical results, we are excited for the opportunity to expand testing of CA-170, possibly in earlier lines of treatment and in a greater number of immunotherapy treatment-naïve cancer patients," commented Mr. CSN Murthy, Chief Executive Officer of Aurigene. "Together with Curis, we have designed a Phase 2 trial, treating selected populations of patients of interest in the CA-170 program to be treated at major cancer centers in India. Aurigene’s decision to sponsor and fund this trial is further affirmation of our commitment to CA-170 and a reflection of the successful collaboration we have with Curis in multiple development programs. Aurigene has the commercial rights to the program in India and Russia in addition to milestones, royalties other commercial supply rights globally."

"We are pleased with these early results. Evidence of tumor shrinkage and multiple patients remaining on drug treatment for extended periods, along with signals for biomarkers of immune modulation in patient blood and tumor samples, tells us the program continues to move in the right direction. We plan to continue with the dose escalation and continued analysis of patient biopsy samples in the Phase 1 trial," said Ali Fattaey, Ph.D., President and Chief Executive Officer of Curis. "We expect to provide additional updates at upcoming conferences including the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting in November."

"The ability for cancer patients to administer a potential checkpoint inhibitor on their own as a once daily oral drug is a significant and unique opportunity in our field," added Adil Daud, M.D., investigator in the CA-170 Phase 1 trial and director of Melanoma Clinical Research at the UCSF Helen Diller Family Comprehensive Cancer Center. "These initial clinical results are encouraging and merit continued development."

10-Q – Quarterly report [Sections 13 or 15(d)]

Exicure has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Exicure, 2017, SEP 12, 2017, View Source [SID1234521881]).

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