On November 8, 2017 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) announced today that Genentech Inc., a member of the Roche Group, obtained approval from the U.S. Food and Drug Administration (FDA), for Alecensa in the treatment of "anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC)" (Press release, Chugai, NOV 8, 2017, View Source [SID1234521712]). In addition to this approval, the FDA also converted Alecensa’s initial accelerated approval (given in December 2015) to a full approval for the treatment of people with ALK-positive, metastatic NSCLC who have progressed on or are intolerant to crizotinib (second-line).

"In July 2014, Alecensa obtained its first approval globally in Japan. With the goal of contributing to many patients in the world, the development of Alecensa was progressed with a focus on speed in each country," said Dr. Yasushi Ito, Chugai’s Senior Vice President, Head of Project & Lifecycle Management Unit. "The results of Phase III studies both in Japan and overseas showed that Alecensa could improve current treatment of ALK-positive NSCLC."

Alecensa received Breakthrough Therapy Designation from the FDA in September 2016 for the treatment of adults with advanced ALK-positive NSCLC who have not received prior treatment with an ALK inhibitor. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible. Breakthrough Therapy designation was granted on the basis of the Japanese phase III J-ALEX study which was conducted prior to ALEX study.

The new approval is based on results from the phase III ALEX study.
The ALEX study evaluates the efficacy and safety of Alecensa compared with crizotinib in people with ALK-positive NSCLC who had not received prior systemic therapy (first-line). In the study, Alecensa significantly reduced the risk of disease worsening or death by 47% (HR=0.53, 95%CI: 0.38-0.73, stratified log-rank test, p<0.0001) compared to crizotinib as assessed by independent review committee. Median progression-free survival (PFS) was 25.7 months (95%CI: 19.9-not estimable) for people who received Alecensa compared with 10.4 months (95%CI: 7.7-14.6) for people who received crizotinib. The safety profile of both drugs was consistent with that observed in previous studies, with no new findings.

In addition, Alecensa significantly reduced the risk of the cancer spreading to or growing in the brain or central nervous system (CNS) compared to crizotinib by 84% (HR=0.16, 95%CI: 0.10-0.28, stratified log-rank test, p<0.0001). This was based on a time to CNS progression analysis in which there was a lower risk of progression in the CNS as the first site of disease progression for people who received Alecensa (12%) compared to people who received crizotinib (45%).

About Alecensa
Alecensa is a highly selective oral ALK inhibitor discovered by Chugai. It has been reported that approximately five percent of patients with NSCLC express a chromosomal rearrangement which leads to fusion of the ALK gene with another gene.1) ALK kinase signalling is constantly active in cells with such fusion genes, resulting in uncontrolled growth of tumour cells and transforming the cells into tumour cells.2, 3) Alecensa exerts its anti-tumour effect by selectively inhibiting ALK kinase activity to inhibit tumour cell proliferation and induce cell death.4) In addition, Alecensa is not recognized by the active efflux system in the blood brain barrier which actively pumps molecules out of the brain. Alecensa is able to remain active in the central nervous system and has proven activity against brain metastases.

Alecensa is currently approved in the United States, Europe, Kuwait, Israel, Hong Kong, Canada, South Korea, Switzerland, India, Australia, Singapore, Taiwan, Liechtenstein, Thailand, Argentina and Turkey for the treatment of people with metastatic (advanced) ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, crizotinib. In Japan, Alecensa is available to patients with "ALK fusion gene positive unresectable, recurrent/advanced NSCLC" and is marketed by Chugai. The approved dosage and administration in Japan is "300mg alectinib administered orally twice daily for adult patient."

1) Biomarker committee of The Japan Lung Cancer Society, Guidelines for ALK gene tests in lung cancer patients
2) Soda et al., Nature. 448: 561-566 (2007)
3) Takeuchi et al., Clin Cancer Res. 15: 3143-3149 (2009)
4) Sakamoto et al., Cancer Cell. 19: 679-690 (2011)

Note: The dosage and administration of the ALEX study is "600mg alectinib administered orally twice daily," which is different from the Japanese dosage and administration.

On November 8, 2017 Bavarian Nordic A/S (OMX: BAVA, OTC: BVNRY) reported its interim financial results in line with guidance for the first nine months of 2017 and business progress for the third quarter of 2017 (Press release, Bavarian Nordic, NOV 8, 2017, View Source [SID1234521694]).

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Third quarter highlights and subsequent events

In October, the Canadian Department of National Defence exercised another option for the procurement of 20,000 doses of IMVAMUNE smallpox vaccine, and has thereby exercised 80,000 doses to-date of the 180,000 doses in the on-going smallpox vaccine framework agreement.
In September, Bavarian Nordic was awarded a contract valued at up to USD 539 million for supply of freeze-dried IMVAMUNE to the U.S. Government
In September, preliminary follow up results from the Phase 2 study of MVA-BN RSV were reported, showing that after six months, a persistent antibody response against RSV could still be observed. Concurrently, the Company announced its plans for initiating a human challenge trial in 2018
In September, the PROSPECT Phase 3 study of PROSTVAC as a monotherapy in metastatic prostate cancer was discontinued after recommendation from the independent Data Monitoring Committee that the study was unlikely to reach its primary endpoint of overall survival.
In July, Bavarian Nordic and Janssen expanded their partnership with an additional worldwide license and collaboration agreement valued up to USD 879 million, granting Janssen the exclusive rights to Bavarian Nordic’s MVA-BN technology for vaccines against hepatitis B virus (HBV) and the human immunodeficiency virus (HIV-1). As part of the license agreement, Johnson & Johnson Innovation – JJDC, Inc. subscribed for 512,102 new shares in Bavarian Nordic in a private placement, raising gross proceeds of DKK 207.5 million.

Financial results

Revenue generated for the nine months ending September 30, 2017 was DKK 1,329 million/USD 211 million (DKK 591 million/USD 94 million in the first nine months of 2016).
The income before interest and tax (EBIT) was a gain of DKK 531 million/USD 84 million (loss of DKK 82 million/USD 13 million in the first nine months of 2016).
As of September 30, 2017 the Group’s cash preparedness was DKK 2,808 million/USD 445 million (DKK 1,647 million/USD 261 million as of September 30, 2016), including unutilized credit lines.

"While the stoppage of the PROSPECT study was a setback in our ambition to develop improved treatment options for patients, our belief in our platform and its capabilities remains as strong as ever. Our company continues to execute on our growth strategy and we continue to see the fruits of our labour, not only with the clinical advancements in RSV and with CV301, but also with the expansion of our partnerships with Janssen and the US Government, ensuring the future growth of the company." said Paul Chaplin, President & Chief Executive Officer of Bavarian Nordic.

Outlook for 2017 maintained
Bavarian Nordic maintains its financial expectations for 2017 as announced July 27, 2017. As only limited revenues are expected in the fourth quarter, the Company still expects revenues of approximately DKK 1,300 million/USD 206 million for the full year, earnings before interest and tax (EBIT) of approximately DKK 350 million/USD 56 million and a cash preparedness at year-end of approximately DKK 2,600 million/USD 412 million.

Danish kroner (DKK) is the Company’s functional currency. All USD figures provided above are based upon an assumed exchange rate of DKK 6.30 per 1.00 USD, which was the exchange rate as of September 30, 2017.

Anticipated selected pipeline developments

H2 2017

Initiate Phase 2 booster-study of MVA-BN RSV in subjects previously vaccinated in the earlier Phase 2 study last year
Initiate Phase 2 of the combination of CV301 and KEYTRUDA in first line NSCLC
Initiate Phase 1 fowlpox booster study of BN-Brachyury

H1 2018

Report top-line results from Phase 3 non-inferiority study of IMVAMUNE
Report results from MVA-BN RSV booster-study
Initiate human challenge study of MVA-BN RSV
Report Phase 1 results of combination of CV301 and OPDIVO
Initiate Phase 2 study of the combination of CV301 and TECENTRIQ in bladder cancer
Emerging results from investigator-sponsored Phase 2 combination trials of PROSTVAC
Report results from Phase 1 booster study of BN-Brachyury

H2 2018

End of Phase 2 meeting with FDA to determine registration pathway for MVA-BN RSV in elderly
Report Phase 2 results (ORR) from combination of CV301 and KEYTRUDA in NSCLC
Initiate Phase 2 study of BN-Brachyury in Chordoma
Initiate Phase 2 study of BN-Brachyury in second indication

Conference call and webcast
The management of Bavarian Nordic will host a conference call today at 2 pm CET (8 am EST) to present the interim results followed by a Q&A session. A listen-only version of the call can be accessed via /investor/events.aspx?event=5051. To join the Q&A session, use one of the following dial-in numbers: Denmark: +45 32 71 16 60, UK: +44 (0) 20 3427 1911, USA: +1 646 254 3364. Participant code is 7659153.

On November 7, 2017 The Institut Curie and Roche reported that they have been collaborating since 2007, particularly in the treatment of breast cancers (Press release, Institut Curie, NOV 7, 2017, View Source [SID1234554040]).

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Since then, other translational research projects have been carried out and have created a strong scientific link between Institut Curie and the Roche Research Centers (gRED and pRED). This framework agreement, which has just been signed for a period of 3 years, is a continuation of more than 10 years of successful scientific collaboration.

Such an agreement facilitates and accelerates the operational implementation of scientific programs conducted in partnership, allowing close interaction between Roche R & D teams and the Institut Curie teams. Collaborations will include the implementation of research projects in partnership or training, stresses Amaury Martin, Director of Technology Transfer and Industrial Partnerships of the Institut Curie and Director of the Institut Carnot Curie Cancer .

The Institut Curie is a major actor in oncology research and Roche is the pioneer of personalized medicine. Our common ambition is to innovate to advance the fight against cancer. Today, the scope of the collaboration focuses on immuno-oncology. Thanks to a better understanding of cancer biology and the mechanisms of antitumor immunity, the research projects initiated in the framework agreement aim at optimizing the development of new treatments in order to allow a greater number of patients to benefit from immunotherapy, says Patrice Denèfle, Director of the Roche Institute.

On November 7, 2017 Alligator Bioscience (Nasdaq Stockholm: ATORX), a biotechnology company developing antibody-based pharmaceuticals for tumor-directed immunotherapy, reported results from a clinical phase I first-in-human study of the drug candidate ADC-1013 (JNJ-64457107), a human, monospecific, agonistic, IgG1 antibody targeting the co-stimulatory receptor CD40 (Press release, Alligator Bioscience, NOV 7, 2017, View Source [SID1234538683]). The study results show that ADC-1013 is generally well tolerated and support further clinical development of ADC-1013 as a mono- or combination therapy. The data will be presented in an oral and poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 32nd Annual Meeting in National Harbor, Maryland, US, on 10 and 11 November 2017.

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"We are very excited about the continued progress and promising early data of ADC-1013", said Per Norlén, CEO at Alligator Bioscience. "The data indicate that it is well tolerated at clinically relevant doses. There is clear evidence supporting activation of CD40 receptors, which together with the clinical observations give us increased confidence for the continued clinical development of ADC-1013."

A total of 23 patients were treated with ADC-1013, either intratumorally or intravenously. Focus on this study was on intratumoral administration, with only five patients receiving ADC-1013 intravenously. Alligator’s partner Janssen Biotech, Inc., is currently performing a phase I dose-escalation study investigating intravenous administration of ADC-1013.

Adverse events throughout the study were primarily fatigue, pyrexia, nausea and vomiting, and were mostly CTCAE Grade 1 or 2 and transient. Intratumoral administration of ADC-1013 into superficial metastases was well tolerated at doses up to at least 400 μg/kg. Two patients experienced dose limiting effects (grade 3 abdominal pain) at 400 μg/kg after injections into deeper (i.e. hepatic) lesions.

Secondary outcome measures on tumor efficacy included a best overall response of stable disease for at least 12 months in one patient who received 400 µg/kg intratumorally into a superficial lesion with intraindividual dose escalation up to 900 µg/kg.

Alligator Bioscience will give both an oral and poster presentation at the SITC (Free SITC Whitepaper) meeting, with the title: "First-in-human study with intratumoral administration of a CD40 agonistic antibody: preliminary results with ADC-1013/JNJ-64457107 in advanced solid malignancies". The oral presentation will be held at session Clinical Trials: New Agents, starting at 1:45 p.m. ET (7:45 p.m. CET) on 10 November 2017. The accompanied study poster will be presented on Saturday 11 November.

For further information about the program, please visit the conference web site: View Source

For further information:
Cecilia Hofvander, Director Investor Relations & Communications
Phone +46 46 286 44 95
E-mail: [email protected].

This release contains information that Alligator Bioscience AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 2:00 p.m. CET on 7 November 2017.

Notes to editors

About ADC-1013
ADC-1013 is a drug candidate intended for immunotherapy of different types of cancer. Pre-clinical data have shown that the ADC-1013 antibody effectively activates T-cells, mediated through binding to the co-stimulatory receptor CD40 on dendritic cells. The increased T-cell activation enables the immune system to attack the cancer. In addition, since some cancer cells express CD40 on the surface, ADC-1013 may act also through a secondary mechanism of action killing cancer cells directly.

In August 2015, Alligator licensed global development rights for ADC-1013 (JNJ-64457107) to Janssen Biotech, Inc. Currently, Janssen Biotech, Inc. performs a phase I dose-escalation clinical study (ClinicalTrials: NCT02829099) with intravenous administration of ADC-1013. This study is ongoing with approximately 50 patients recruited to date.

About the ADC-1013 intratumoral clinical phase I study
The study to be presented is a multicenter, open-label phase I study in patients with late stage solid tumors no longer responding to standard treatment evaluating safety and tolerability, pharmacokinetics, immunogenicity, biomarker response and clinical response. The study is a dose-escalation study, involving intratumoral (22.5-400 µg/kg) and intravenous (75 µg/kg) administration of ADC-1013 at five hospitals in Sweden, Denmark and the UK. The study was performed by Alligator and includes 24 enrolled patients and ten different tumor types. For further information, please visit View Source; NCT02379741.

On November 7, 2017 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage pharmaceutical company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology targets for the treatment of cancer reported that initial data from the ongoing trial of CB-839 in combination with Opdivo in patients with melanoma, renal cell carcinoma and non-small cell lung cancer will be presented Saturday, November 11th, 2017, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, Calithera Biosciences, NOV 7, 2017, View Source [SID1234535250]). Calithera also announced it has expanded its existing clinical collaboration with Bristol-Myers Squibb, evaluating CB-839 in combination with Opdivo. CB-839 is an orally bioavailable glutaminase inhibitor currently in Phase 2 trials, and Opdivo is a PD-1 immune checkpoint inhibitor designed to overcome immune suppression.

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"This trial is designed to include patients who are currently receiving checkpoint inhibitor therapy and experiencing disease progression at the time of enrollment. There is significant unmet need among these patients, and the responses observed would not be expected with treatment with Opdivo alone in this population," said Susan M. Molineaux, Ph.D., founder, Chief Executive Officer and President of Calithera Biosciences. "The expanded clinical collaboration with Bristol-Myers Squibb will help us pursue our strategy of developing CB-839 in combination with Opdivo with the hope of improving treatment options for patients with cancer."

Calithera is conducting a Phase 1/2 trial (NCT02771626) in collaboration with Bristol-Myers Squibb designed to evaluate the safety, tolerability and efficacy of CB-839 in combination with Opdivo in patients with renal cell carcinoma, melanoma or non-small cell lung cancer. The study will be expanded to enroll additional melanoma patients. As part of the expanded collaboration, melanoma development costs will be shared, and a joint development committee will be established to guide the development and regulatory strategy.

The ongoing study enrolled three cohorts of patients who have received a checkpoint inhibitor (PD-1/PD-L1) in the most recent line of therapy.

Among 16 evaluable melanoma patients, all of whom were progressing on a checkpoint inhibitor at study entry, one patient achieved a complete response and two patients achieved partial responses. The overall response rate in this cohort was 19%, and the overall disease control rate was 44%.
Among six evaluable non-small cell lung cancer patients, all of whom were progressing on a checkpoint inhibitor at study entry, 67% experienced stable disease.
Among eight evaluable renal cell carcinoma patients, 75% were progressing and 25% had stable disease at study entry.

Stable disease was achieved in 75%, all of whom were progressing on a checkpoint inhibitor at study entry. The study enrolled one cohort of renal cell carcinoma patients who have received a checkpoint inhibitor in any prior line of therapy, but never achieved a response to checkpoint therapy.

Among seven evaluable checkpoint inhibitor experienced renal cell carcinoma patients, with a median of four prior lines of therapy, 57% experienced stable disease.

The study enrolled one cohort of renal cell carcinoma patients who were previously treated with VEGF inhibiting therapy, and were naïve to checkpoint inhibitors. Among 19 evaluable checkpoint inhibitor naïve renal cell carcinoma patients, four patients (21%) achieved a partial response and disease control rate was 74%. Fifty percent of the enrolled patients remain on study treatment.

An analysis of all safety evaluable patients demonstrated that CB-839 was well tolerated when combined with Opdivo in melanoma, renal cell carcinoma and non-small cell lung cancer patients. During dose escalation of the combination therapy, there was one report of dose limiting Grade 3 ALT increase, however no maximum tolerated dose was reported. The majority of adverse events reported have been mild to moderate with the most common being fatigue, nausea and photophobia. With 3.7% immune-related adverse events Grade ≥ 3, the data suggest there was no apparent increase in the rate or severity of immune related events compared to historical rates.

Dr. Funda Meric-Bernstam from MD Anderson Cancer Center will present the results on Saturday, November 11, 2017, in an oral and poster session (Abstract #O16), "A phase 1/2 study of CB-839, a first-in-class glutaminase inhibitor, combined with nivolumab in patients with advanced melanoma, renal cell carcinoma or non-small cell lung cancer." The oral presentation slides and the poster will be available on the Company’s website in the publication section at View Source

Calithera will webcast a clinical update on CB-839 on Saturday, November 11th at 3:30 p.m. Pacific Time/ 6:30 p.m. Eastern Time. The call can be accessed by dialing (855) 783-2599 (domestic) or (631) 485-4877 (international), and referring to conference ID 1878409. To access the live audio webcast or the subsequent archived recording, visit the Investors section of the Calithera website at www.calithera.com. The webcast will be recorded and available for replay on Calithera’s website for 30 days.

About CB-839
Calithera’s lead product candidate, CB-839, is a potent, selective, reversible and orally bioavailable inhibitor of glutaminase. CB-839’s onco-metabolism activity takes advantage of the unique metabolic requirements of tumor cells and cancer-fighting immune cells such as cytotoxic T-cells. It is currently being evaluated in Phase 2 clinical trials in multiple tumor types, in combination with standard of care agents.