On September 20, 2018 Array BioPharma Inc. (NASDAQ: ARRY) reported that the European Commission (EC) has approved BRAFTOVI in combination with MEKTOVI for the treatment of adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation, as detected by a validated test (Press release, Array BioPharma, SEP 20, 2018, View Source [SID1234529528]). This approval is applicable to all 28 European Union (EU) member states, as well as Liechtenstein, Iceland and Norway.

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"With an even greater number of patients with advanced BRAF-mutant melanoma in Europe than in the U.S., we are delighted BRAFTOVI + MEKTOVI will be available to these patients who are in critical need of additional options that delay disease progression and improve overall survival," said Ron Squarer, Chief Executive Officer. "Our European partner, Pierre Fabre, has a strong legacy in oncology, and with over a thousand employees dedicated to this therapeutic area, we are very pleased they have made BRAFTOVI + MEKTOVI a top priority for their team."

The EC approval is based on results from the Phase 3 COLUMBUS trial, of which the primary endpoint was median progression-free survival (mPFS). BRAFTOVI + MEKTOVI achieved an mPFS of nearly 15 months [14.9 months versus vemurafenib monotherapy at 7.3 months; hazard ratio (HR) 0.54 (95% CI, 0.41–0.71), p<0.0001].

BRAFTOVI + MEKTOVI is the first targeted treatment to achieve over 30 months median overall survival (OS). As published in The Lancet Oncology in September 2018, BRAFTOVI + MEKTOVI reduced the risk of death compared to vemurafenib [HR (0.61), (95% CI 0.47,0.79), p <0.0001]. Median OS was 33.6 months for patients treated with the combination, compared to 16.9 months for patients treated with vemurafenib.

Detailed recommendations for the use of these products in the EU are described in the summary of product characteristics (SmPC), which are published in the European public assessment report (EPAR) and made available in all official EU languages at View Source

Array has exclusive rights to BRAFTOVI and MEKTOVI in the U.S. and Canada. Array has granted Ono Pharmaceutical exclusive rights to commercialize both products in Japan and South Korea, Medison exclusive rights to commercialize both products in Israel and Pierre Fabre exclusive rights to commercialize both products in all other countries, including Europe, Latin America and Asia (excluding Japan and South Korea).

In June 2018, the U.S. Food and Drug Administration (FDA) approved BRAFTOVI + MEKTOVI for the treatment of unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test. BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma.

Only 5% of patients who received BRAFTOVI + MEKTOVI discontinued treatment due to adverse reactions. The most common adverse reactions (≥25%) in patients receiving BRAFTOVI + MEKTOVI were fatigue, nausea, diarrhea, vomiting, abdominal pain, and arthralgia.

About BRAF-mutant Metastatic Melanoma
Melanoma develops when unrepaired DNA damage to skin cells triggers mutations that may lead them to multiply and form malignant tumors. Metastatic melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates. [1,2] There are a variety of gene mutations that can lead to metastatic melanoma. The most common genetic mutation in metastatic melanoma is BRAF. There are about 200,000 new cases of melanoma diagnosed worldwide each year, approximately half of which have BRAF mutations, a key target in the treatment of metastatic melanoma. [1-5]

About BRAFTOVI + MEKTOVI
BRAFTOVI is an oral small molecule BRAF kinase inhibitor and MEKTOVI is an oral small molecule MEK inhibitor which target key enzymes in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of proteins in this pathway has been shown to occur in many cancers including melanoma, colorectal cancer, non-small cell lung cancer and others. In the U.S., BRAFTOVI + MEKTOVI are approved for the treatment of unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test. BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma. In Europe, the combination is approved for adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation, as detected by a validated test.

The Swiss Medicines Agency (Swissmedic) and the Australian Therapeutic Goods Administration (TGA) are currently reviewing the Marketing Authorization Applications for BRAFTOVI and MEKTOVI submitted by Pierre Fabre, and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) is currently reviewing the Manufacturing and Marketing Approval applications submitted by Ono Pharmaceutical Co, Ltd.

About COLUMBUS
The COLUMBUS trial (NCT01909453) is a two-part, international, randomized, open label Phase 3 trial evaluating the efficacy and safety of BRAFTOVI (encorafenib) in combination with MEKTOVI (binimetinib) compared to vemurafenib and encorafenib monotherapy in 921 patients with locally advanced, unresectable or metastatic melanoma with BRAFV600 mutation. The primary endpoint of the trial was mPFS; all secondary efficacy analyses, including the prospectively planned analysis overall survival, are descriptive in nature. Over 200 sites across North America, Europe, South America, Africa, Asia and Australia participated in the trial.

BRAFTOVI + MEKTOVI Indications and Usage
BRAFTOVI (encorafenib) and MEKTOVI (binimetinib) are kinase inhibitors indicated for use in combination for the treatment of adult patients with unresectable or metastatic melanoma with a BRAFV600E mutation.
Limitations of Use: BRAFTOVI is not indicated for the treatment of patients with wild-type BRAF melanoma.

BRAFTOVI + MEKTOVI Important Safety Information
The information below applies to the safety of the combination of BRAFTOVI and MEKTOVI unless otherwise noted.

Warnings and Precautions
New Primary Malignancies: New primary malignancies, cutaneous and non-cutaneous malignancies can occur. In the COLUMBUS trial, cutaneous squamous cell carcinoma, including keratoacanthoma, occurred in 2.6% and basal cell carcinoma occurred in 1.6% of patients. Perform dermatologic evaluations prior to initiating treatment, every 2 months during treatment, and for up to 6 months following discontinuation of treatment. Discontinue BRAFTOVI for RAS mutation-positive non-cutaneous malignancies.

Tumor Promotion in BRAF Wild-Type Tumors: Confirm evidence of BRAFV600E or BRAFV600Kmutation prior to initiating BRAFTOVI.

Cardiomyopathy: In the COLUMBUS trial, cardiomyopathy occurred in 7% and Grade 3 left ventricular dysfunction occurred in 1.6% of patients. Cardiomyopathy resolved in 87% of patients. Assess left ventricular ejection fraction by echocardiogram or MUGA scan prior to initiating treatment, 1 month after initiating treatment, and then every 2 to 3 months during treatment. The safety has not been established in patients with a baseline ejection fraction that is either below 50% or below the institutional lower limit of normal.

Venous Thromboembolism (VTE): In the COLUMBUS trial, VTE occurred in 6% of patients, including 3.1% of patients who developed pulmonary embolism.

Hemorrhage: In the COLUMBUS trial, hemorrhage occurred in 19% of patients and ≥Grade 3 hemorrhage occurred in 3.2% of patients. Fatal intracranial hemorrhage in the setting of new or progressive brain metastases occurred in 1.6% of patients.

Ocular Toxicities: In the COLUMBUS trial, serous retinopathy occurred in 20% of patients; 8% were retinal detachment and 6% were macular edema. Symptomatic serous retinopathy occurred in 8% of patients with no cases of blindness. In patients with BRAF mutation-positive melanoma across multiple clinical trials, 0.1% of patients experienced retinal vein occlusion (RVO). Permanently discontinue MEKTOVI in patients with documented RVO. In COLUMBUS, uveitis, including iritis and iridocyclitis, was reported in 4% of patients. Assess for visual symptoms at each visit. Perform ophthalmic evaluation at regular intervals and for any visual disturbances.

Interstitial Lung Disease (ILD): ILD, including pneumonitis, occurred in 0.3% of patients with BRAF mutation-positive melanoma across multiple clinical trials. Assess new or progressive unexplained pulmonary symptoms or findings for possible ILD.

Hepatotoxicity: In the COLUMBUS trial, the incidence of Grade 3 or 4 increases in liver function laboratory tests was 6% for alanine aminotransferase (ALT) and 2.6% for aspartate aminotransferase (AST). Monitor liver laboratory tests before and during treatment and as clinically indicated.

Rhabdomyolysis: In the COLUMBUS trial, elevation of laboratory values of serum creatine phosphokinase (CPK) occurred in 58% of patients. Rhabdomyolysis was reported in 0.1% of patients with BRAF mutation-positive melanoma across multiple clinical trials. Monitor CPK periodically and as clinically indicated.

QTc Prolongation: In the COLUMBUS trial, an increase in QTcF to >500 ms was measured in 0.5% (1/192) of patients. Monitor patients who already have or who are at significant risk of developing QTc prolongation. Correct hypokalemia and hypomagnesemia prior to and during BRAFTOVI administration. Withhold, reduce dose, or permanently discontinue for QTc >500 ms.

Embryo-Fetal Toxicity: BRAFTOVI or MEKTOVI can cause fetal harm when administered to pregnant women. Nonhormonal contraceptives should be used during treatment and for at least 30 days after the final dose for patients taking BRAFTOVI + MEKTOVI.

Adverse Reactions
The most common adverse reactions (≥20%, all Grades, in the COLUMBUS trial) were: fatigue, nausea, diarrhea, vomiting, abdominal pain, arthralgia, myopathy, hyperkeratosis, rash, headache, constipation, visual impairment, serous retinopathy.

In the COLUMBUS trial, the most common laboratory abnormalities (≥20%, all Grades) included: increased creatinine, increased CPK, increased gamma glutamyl transferase, anemia, increased ALT, hyperglycemia, increased AST, and increased alkaline phosphatase.

Drug interactions
Avoid concomitant use of strong or moderate CYP3A4 inhibitors or inducers and sensitive CYP3A4 substrates with BRAFTOVI. Modify BRAFTOVI dose if concomitant use of strong or moderate CYP3A4 inhibitors cannot be avoided.

Please see full Prescribing Information for BRAFTOVI and full Prescribing Information for MEKTOVI for additional information [6,7]. You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Array at 1-844-Rx-Array (1-844-792-7729).

On September 20, 2018 Cell Medica reported the treatment of the first patient world-wide to receive CMD-501, an autologous CAR-NKT therapy targeting pediatric neuroblastoma (Press release, Cell Medica, SEP 20, 2018, View Source [SID1234530199]). This is the first time an engineered NKT cell therapy has been used in humans. Cell Medica is a clinical-stage biopharmaceutical company that is transforming the treatment of solid and hematological cancer by developing the next generation of CAR therapies.

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This open-label Phase 1 study, GINAKIT2, is being carried out in collaboration with both Baylor College of Medicine (BCM) and Texas Children’s Hospital.

Dr. Andras Heczey, Principal Investigator, Assistant Professor, Pediatrics-Oncology at Baylor College of Medicine and Physician-Scientist, Texas Children’s Cancer Center commented: "Dosing the first patient with this novel CAR-NKT therapy is an important milestone for all pediatric patients with neuroblastoma. CAR-NKTs may offer an exciting new therapeutic option for these patients and potentially for others with solid and hematological cancers. I am extremely grateful to the patients and families participating in this ground-breaking study."

Chris Nowers, Cell Medica’s CEO, said: "We believe that our CAR-NKT platform has a unique profile, with a potential to target solid and hematological tumors, as well as the possibility of a subsequent allogeneic "off the shelf" CAR-NKT therapy that could address some challenges of current autologous CAR-T therapies. This study marks an important step forward for Cell Medica and we are proud to be leading the development of this innovative class of next generation CAR therapies with our colleagues at BCM and Texas Children’s."

Innovative CAR-NKT Platform
CMD-501 is based on Cell Medica’s novel CAR-NKT platform, a next-generation technology of engineered immune cells with enhanced functions for the treatment of hematological and solid tumors, utilizing the unique properties of NKT cells, a specialized type of innate lymphocytes, sharing properties of T and NK cells. CMD-501 is the initial study from Cell Medica’s CAR-NKT pipeline and utilizes an autologous approach. The patient’s own NKT cells are genetically engineered with a CAR targeting GD2, a molecule expressed on the surface of nearly all neuroblastoma cells. In collaboration with its partners at BCM and Texas Children’s, Cell Medica designed this CAR-NKT cell therapy to also secrete the cytokine IL-15, which has been shown in pre-clinical studies to increase the persistence of CAR-NKT cells and improve their efficacy within the immunosuppressive tumor microenvironment.

Dr. Leonid Metelitsa, Professor of Pediatrics, Hematology-Oncology, Baylor College of Medicine and Co-Director, Neuroblastoma Program, Texas Children’s Cancer Center added: "It has been a great pleasure leading the multi-disciplinary team in the development of this versatile CAR-NKT platform. NKT cells effectively traffic to the tumor site, so expressing tumor-specific CARs in these cells ensures delivery to the site of disease for maximum efficacy. We’re now exploiting another natural feature of NKT cells, their lack of allo-reactivity and we are developing allogeneic, "off the shelf", therapies that will further harness the unique advantages of NKT cells."

First-in-Human Study
GINAKIT2 is a first-in-human, dose escalation evaluation of CMD-501 in children with relapsed or refractory (R/R) high-risk neuroblastoma, (NCT03294954). Neuroblastomas occur primarily in children and account for 7-10 percent of all pediatric cancers. Ninety percent of patients are younger than 5 years at diagnosis. R/R high risk neuroblastoma is one of the deadliest types of childhood cancer and the current median survival is around 1-3 years. Almost all neuroblastomas express GD2, which is targeted by CMD-501. This study is supported by a grant from Alex’s Lemonade Stand Foundation (ALSF), awarded to BCM investigators, Drs. Heczey and Metelitsa.

About Neuroblastoma and GD2
Neuroblastoma is a cancer of the sympathetic nervous system which can occur in the chest, neck, abdomen and adrenal glands, and can metastasize to the bone marrow and other organs. Children with low or intermediate risk neuroblastoma can be cured through surgical intervention and/or chemotherapy, however, at least half of all children with neuroblastoma have high risk disease, which often requires combined surgical, radio-, immuno-, and chemotherapy, in addition to autologous stem cell transplantation. Patients with relapsed/refractory high-risk neuroblastoma have one of the deadliest types of childhood cancer and a poor prognosis, with median survival of 1-3 years.

GD2 is a molecule expressed on tumors of neuroectodermal origin, including almost all neuroblastomas, and a substantial fraction of small cell lung cancer and melanoma, with restricted expression on normal tissues, making it a good target for CAR-NKT cell therapy.

About CMD-501
CMD-501 is an innovative autologous product in which NKT cells are genetically engineered with a CAR targeting GD2. NKT cells are a subset of T lymphocyte with the cytotoxic and anti-tumor properties of conventional T cells, but with other biological attributes that are expected to improve their ability to attack tumors. GD2 is a molecule expressed on the surface of most neuroblastoma cells.

In collaboration with its partners at BCM, Cell Medica has engineered a GD2-specific CAR construct that is additionally designed to secrete the cytokine IL-15, which has been shown in pre-clinical studies to increase the persistence of CAR-NKT cells and improve their efficacy within the immunosuppressive tumor microenvironment. CMD-501 is an autologous product, meaning that each patient’s own cells are collected, modified and activated outside the body, and then infused back into the same patient. However, NKT cells also have significant potential for so-called off-the-shelf use, where cells from a healthy donor could be prepared in large quantities in advance and used to treat many different patients. Cell Medica is collaborating with BCM to bring an off-the-shelf CAR-NKT cell product into the clinic in the near future.

On September 20, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that it has entered into a clinical trial collaboration agreement with a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, U.S.A., known as MSD outside the United States and Canada, to evaluate the combination of Daiichi Sankyo’s investigational HER2 targeting antibody drug conjugate DS-8201 and KEYTRUDA (pembrolizumab) in HER2 expressing advanced/metastatic breast and HER2 expressing or HER2 mutant non-small cell lung cancers (NSCLC) (Press release, Daiichi Sankyo, SEP 20, 2018, View Source [SID1234529511]).

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"We are excited to pursue this opportunity to evaluate the safety, tolerability and activity of DS-8201 in combination with KEYTRUDA and whether this combination may provide a potential new treatment approach for patients with HER2 expressing advanced breast and non-small cell lung cancer," said Tom Held, Vice President, Head, Antibody Drug Conjugate Task Force, Oncology Research and Development, Daiichi Sankyo. "Strategic collaborations like this support our goal to pursue, investigate and maximize the application of DS-8201 in combination with other compounds that target different pathways to address unmet needs of patients with cancer."

About the Study

Under the terms of the agreement, Daiichi Sankyo will conduct a two-part phase 1b multicenter, open-label study to:

・ Determine the safety, tolerability and dose of DS-8201 in combination with KEYTRUDA and evaluate efficacy of the combination in patients with HER2 expressing advanced/metastatic breast cancer and patients with HER2 expressing or HER2 mutant advanced/metastatic NSCLC.

・ Enroll patients into one of four cohorts: patients with HER2 positive advanced breast cancer who have been previously treated with ado-trastuzumab emtansine (T-DM1) (cohort 1); patients with HER2 low expressing advanced breast cancer (IHC 1+ or IHC 2+/ISH-) who have received available standard of care (cohort 2); patients with HER2 expressing advanced NSCLC (IHC 1+, 2+, or 3+) who have not received prior treatment with anti-PD-1 or anti-PD-L1 agents (cohort 3); and patients with HER2 mutant advanced NSCLC who have not received prior treatment with anti-PD-1 or anti-PD-L1 agents (cohort 4).

The primary endpoints of the study are maximum tolerated dose/recommended expansion dose and overall response rate. Secondary endpoints include duration of response, disease control rate, progression-free survival, overall survival, time to response and safety. The study is expected to enroll approximately 125 patients in the U.S. and Europe. Additional details of the agreement were not disclosed.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

About DS-8201

DS-8201 is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary ADC technology, DS-8201 is comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

DS-8201 is currently in pivotal phase 2 clinical development for HER2 positive unresectable and/or metastatic breast cancer resistant or refractory to T-DM1 (DESTINY-Breast01) in North America, Europe and Asia; pivotal phase 2 development for HER2 positive advanced gastric cancer resistant or refractory to trastuzumab (DESTINY-Gastric01) in Japan and South Korea; phase 2 development for HER2 expressing advanced colorectal cancer in North America, Europe and Japan; phase 2 development for unresectable and/or metastatic non-squamous HER2 overexpressing or HER2 mutated non-small cell lung cancer (NSCLC) in North America, Europe and Japan; and phase 1 development for other HER2 expressing advanced/unresectable or metastatic solid tumors in the U.S. and Japan.

DS-8201 has been granted Breakthrough Therapy designation for the treatment of patients with HER2 positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1), and Fast Track designation for the treatment of HER2 positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2 targeted therapies including T-DM1 by the U.S. Food and Drug Administration. DS-8201 has also been granted SAKIGAKE Designation by the Japan Ministry of Health, Labour and Welfare for the treatment of HER2 positive advanced gastric or gastroesophageal junction cancer.

DS-8201 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

On September 20, 2018 Compugen Ltd. (Nasdaq: CGEN), a clinical-stage cancer immunotherapy company and leader in predictive target discovery, reported that it was informed that Bayer AG dosed the first patient in the Phase 1 clinical trial of BAY 1905254, a first-in-class immuno-oncology therapeutic antibody targeting the ILDR2 protein, in patients with advanced solid tumors (Press release, Compugen, SEP 20, 2018, View Source [SID1234529531]). Under the terms of the collaboration and license agreement, Compugen is entitled to a milestone payment of $7.8 million at first patient dosing. ILDR2 is a new immune checkpoint protein identified by Compugen using its predictive target discovery platform.

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"ILDR2 was one of the first immune checkpoint targets discovered through our discovery platforms and the first to enter into a R&D collaboration and license agreement with a pharma partner," stated Anat Cohen-Dayag, PhD, President and CEO of Compugen. "Bayer has been an outstanding partner and we greatly appreciate their excellent R&D team and commitment to advancing this program to the clinic."

"BAY 1905254 and our internally-developed COM701 are the first drug candidates to enter Phase 1 trials addressing new drug targets discovered computationally by Compugen. This represents a breakthrough achievement for Compugen and proof-of-concept of the power of our computational discovery capabilities. We hope that each of these drug candidates will become a life changing treatment option for patients unresponsive to existing cancer immunotherapies," Dr. Cohen-Dayag added.

About ILDR2 and BAY 1905254
ILDR2 is a novel B7/CD28-like immune checkpoint target discovered computationally by Compugen. Preclinical studies demonstrated inhibitory effects of ILDR2 on T cells, consistent with it being an immune checkpoint ligand. Additional expression and functional studies suggest that ILDR2 acts as an inhibitor of the priming step of T cell activation, thereby muting T cell response to cancer.

BAY 1905254 is a fully human antibody that blocks the immunosuppressive activity of ILDR2. BAY 1905254 exhibits anti-tumor activity as a monotherapy in various mouse models, and also demonstrates additive anti-tumor effects in combination with other cancer therapy approaches in those models, indicating the possibility for multiple combination uses in cancer immunotherapy.

On September 19, 2018 Transgene (Paris:TNG) (Euronext Paris: TNG), Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancers and infectious diseases, reported its financial results for the six-month period ended June 30, 2018, and provides an update on its clinical and preclinical portfolio (Press release, Transgene, SEP 19, 2018, View Source [SID1234529493]).

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Philippe Archinard, Chairman and Chief Executive Officer of Transgene, commented:

"2018 is a period of intense activity for Transgene. We obtained $48 million in the form of Tasly Biopharmaceuticals shares following the sale of TG1050 and TG6002 rights in Greater China. We presented new results on our oncolytic virus Pexa-Vec at ASCO (Free ASCO Whitepaper) that benefitted from a positive reception. We have continued to make progress with our clinical and preclinical programs.

Looking ahead we expect to announce more comprehensive clinical results from our strategic studies before the end of 2018 and over the course of 2019.

Our research efforts are focused on our world-leading viral vector expertise applied to our two core technologies: oncolytic viruses and therapeutic vaccines. With our Invir.IOTM platform, we are designing new viruses to provide a better modulation of the tumor micro-environment. We are also about to present our ambitious approach in neoantigen-based therapeutic vaccines at a scientific congress in the coming weeks.

The progress that we have made in 2018 further confirms Transgene’s strategic position as leading innovator in the fight against cancer."

Clinical Pipeline Review

1. Update on company-sponsored strategic trials

Transgene has been making significant progress with its key clinical trials, which are aimed at generating proof-of-concept clinical data. Positive results from these trials would create significant partnering opportunities.

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

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

Trial of TG4010 in combination with nivolumab and with chemotherapy in patients whose tumor cells express low or undetectable levels of PD-L1.

✓ Collaboration deal signed with Bristol-Myers Squibb, for the supply of nivolumab.

✓ Centers open in Europe and the US.

✓ First patient treated in January 2018. Recruitment is progressing with the opening of additional centers; expected completion in 2Q 2019.

→ Evaluation of the primary endpoint (ORR) on all patients (n=35) expected in 2H 2019.

Pexa-Vec
+ sorafenib
(PHOCUS)
Phase 3

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

✓ Clinical trial being conducted by Transgene’s partner, SillaJen, Inc. (sponsor).

✓ Ongoing global recruitment. First patient treated in China (September 2018).

→ First data readout expected in 2019.

Pexa-Vec
+ Opdivo (ICI)
(nivolumab)
Phase 1/2

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

✓ Several active trial sites in France and Italy.

→ Safety review committee expected before year-end 2018.

→ Interim analysis on 15 patients expected mid-2019 (primary endpoint: ORR).

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

HPV-positive cancers including oropharyngeal 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).

✓ Following positive safety evaluation of the combination regimen, Phase 2 part is ongoing and additional sites are being activated in Europe.

→ Phase 1 part results in 4Q 2018 (n=9 patients).

→ Next clinical readout expected in 2H 2019.

TG6002
Phase 1/2a

Gastro-intestinal adenocarcinoma (colon cancer)

✓ TG6002 is an oncolytic virus that produces chemotherapy (5-FU) in the tumor.

✓ Principal investigator: Prof. Philippe Cassier, Centre Léon Bérard, Lyon (France).

✓ Multi-center trial; INDs granted in Belgium, France and Spain.

→ First patient to be treated in the coming weeks.

TG1050
+ Standard of care
Phase 1

Chronic hepatitis B

✓ Trial completed.

→ Full results to be presented at a major liver conference in 4Q 2018.

2. Update on investigator-sponsored trials evaluating Transgene’s products

Transgene is collaborating with leading physicians at world-renowned clinical centers to identify and evaluate novel treatment regimens based on the initiative of the clinicians. These trials are designed to generate further clinical data demonstrating the value of Transgene’s products in exploratory clinical settings. These trials also contribute to strengthening the data packages and increase the visibility of the products amongst the medical community.

TG4010
+ Opdivo (ICI)
(nivolumab)
Phase 2

Non-small cell lung cancer (NSCLC) – 2nd line

Trial of TG4010 in combination with nivolumab (supplied by Bristol-Myers Squibb) in a collaborative agreement with UC Davis Medical Center (USA); principal investigator: Dr. Karen Kelly; sponsor: UC Davis.

✓ The prevailing use of ICIs in first-line therapy in the USA has led to a very significant slowdown in the recruitment of this trial, as patients previously treated with ICIs are excluded per protocol.

✓ Based on Dr. Kelly’s recommendation, the trial will be discontinued due to poor patient accrual.

✓ No unexpected safety issues have been observed.

Pexa-Vec
Neo-adjuvant

Solid tumors

✓ Principal investigator: Prof. Alan Anthoney; sponsor: University of Leeds (UK).

✓ Completion of the recruitment (9 patients).

✓ First positive results presented at the ASCO (Free ASCO Whitepaper) conference in June 2018, confirming strong anti-tumor immunity after intravenous administration. Of the four evaluable patients with liver metastases, one showed complete tumor pathological response at the time of surgery.

✓ The final data from this trial will be published in an upcoming paper and will be presented at a future scientific conference.

✓ Data support ongoing development of Transgene’s Vaccinia virus-based oncolytics.

Pexa-Vec
+ Yervoy (ICI)
(ipilimumab)
Phase 1

Solid tumors (ISI-JX)

✓ Coordinating investigator: Dr. Aurélien Marabelle; sponsor: Centre Léon Bérard, Lyon.

✓ The combination regimen was well tolerated to-date.

✓ Additional sites are being activated.

Pexa-Vec
+ metronomic
cyclophosphamide
Phase 1/2a

HER2 negative breast cancer and soft tissue sarcoma (METROmaJX)

✓ Principal investigator: Prof. Antoine Italiano (Institut Bergonié, Bordeaux); sponsor: INCa (French national cancer institute).

✓ The combination regimen was well tolerated.

✓ At the interim analysis of the patients treated for soft tissue sarcoma, the pre-specified primary endpoint was not reached; enrolment for this indication has been discontinued.

TG6002
Phase 1/2a

Glioblastoma

✓ Principal investigator: Prof. Ahmed Idbahi (AP-HP, Paris), with the support of INCa; sponsor: AP-HP.

✓ Single-center trial.

✓ No safety issues have been observed to-date.

Sale of the Rights of TG1050 and TG6002 in Greater China

On July 10, 2018, Transgene entered into a set of agreements with Tasly Biopharmaceuticals Co., Ltd. under which Transgene sold both the T101 Greater China patent rights and its entire 50% stake in the Transgene Tasly (Tianjin) BioPharmaceuticals Co. Ltd. joint venture which already owned the T601 Greater China patent rights. Following these agreements, Tasly Biopharmaceuticals now holds all rights to research, development and commercialization for T601 and T101 in Greater China.

In return, Transgene received a total of 27.4 million new Tasly Biopharmaceuticals shares valued at $48 million based on the subscription price in pre-IPO financing round of Tasly Biopharmaceuticals, which took place concurrently with the transaction with Transgene. Transgene’s stake represents 2.53% of Tasly Biopharmaceutical’s expanded share capital. Tasly Biopharmaceuticals has announced its intention to list its shares on the Hong Kong Stock Exchange.

The transactions were finalized in August 2018.

NB: T601 and T101 are products developed in China and respectively incorporating Transgene’s TG6002 and TG1050 patented technologies.

Research and preclinical portfolio

In the first half of 2018, Transgene significantly reinforced its preclinical capabilities, capitalizing on its leading viral vectors expertise in the most attractive fields of onco-immunotherapy.

With Invir.IOTM, Transgene is making progress in the increasingly attractive field of novel oncolytic viruses (OVs). The Invir.IOTM platform aims at generating multifunctional novel oncolytic viruses that incorporate several transgenes encoding for a range of specific anticancer weapons and that are capable of better modulating the tumor micro-environment.
The Company is currently evaluating several preclinical Invir.IOTM OV candidates to identify the most attractive one to progress into clinical development. Current candidates include OVs encoding an anti-CTLA-4 antibody in a collaboration with BioInvent, as well as other anti-cancer agents (ligands, cytokines, chemokines, enzymes, etc.). Transgene is on track to initiate the first clinical trial with the first Invir.IOTM designed virotherapy in 2019.

Transgene will shortly be presenting an ambitious personalized immunotherapy approach that will allow the Company to enter the promising field of personalized medicine. This approach combines the Company’s expertise in therapeutic vaccines with neoantigen vectorization and artificial intelligence.
Transgene will provide further updates on preclinical activities in the coming months, including at key upcoming immunotherapy congresses.

Key Financials

Operating revenues amounted to €3.6 million for the first six months of 2018 compared to €3.9 million for the same period in 2017.

Revenues from collaboration and licensing agreements amounted to €0.6 million for the first six months of 2018 versus €0.5 million in the same period in 2017.
The research tax credit amounted to €2.8 million for the first half of 2018, compared to €3.0 million for the first half of 2017.
Research and Development (R&D) expenses amounted to €13.8 million in the first half of 2018 compared to €16.9 million for the same period in 2017. This decrease was mainly due to the 2017 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 trial). External expenses for clinical projects increased by €0.5 million to €3.7 million as we continued to progress the development of all our products.

General and administrative expenses were stable at €3.0 million for the first half of 2018 compared to €3.1 million for the same period in 2017.

Net loss amounted to €14.9 million for the first half of 2018 compared to €18.3 million for the same period in 2017.

As of June 30, 2018, the Company’s cash, cash equivalents, available-for-sale financial assets and other financial assets amounted to €33.1 million versus €41.4 million as of December 31, 2017.

Transgene’s cash burn amounted to €8.4 million in the first half of 2018, compared with €12.3 million for the same period in 2017 (mainly due to the milestone payment of €3.8 million ($4 million) to SillaJen, Inc. in 2017).

Transgene confirms its net cash burn target of approximately €25 million for 2018.

"Our results for the first six months of 2018 are in line with our expectations. We confirm our financial visibility for the next 12 months, excluding the monetization of the Tasly Biopharmaceuticals shares," commented Jean-Philippe Del, Chief Financial Officer of Transgene.

The Board of Directors of Transgene met on September 19, 2018 and adopted the financial statements for the six-month period ended June 30, 2018. The Statutory Auditors have conducted a limited review of the interim consolidated financial statements. The half-year financial report is available on Transgene’s website, View Source