On November 9, 2018 BioXcel Therapeutics, Inc. ("BTI") (Nasdaq: BTAI), a clinical stage biopharmaceutical development company utilizing novel artificial intelligence approaches to identify the next wave of medicines across neuroscience and immuno-oncology, reported quarterly results for the third quarter ended September 30, 2018 and provided an update on key strategic and operational initiatives (Press release, BioXcel Therapeutics, NOV 9, 2018, View Source [SID1234531025]).

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During the third quarter of 2018, the Company made several advances in the development of its two lead clinical programs, BXCL501, a proprietary sublingual thin film formulation of dexmedetomidine (Dex), and BXCL701, an orally-available systemic innate-immune activator.

Third Quarter 2018 and Recent Highlights:

(BXCL501)-Neuroscience Program-

A first-in-human pharmacokinetic (bioavailability) and safety study for the sublingual thin film formulation of Dex is expected to be initiated by the end of 2018 following approval of the investigational new drug (IND) application;

Received valuable feedback and guidance on further development of BXCL501 during a pre-investigational new drug meeting with FDA;

Appointed a clinical research organization (CRO) to support the company in conducting and managing clinical studies;

Completed manufacturing of Company’s proprietary sublingual thin film formulation of Dex, and the drug is available for clinical studies;

Data readout from the pharmacokinetic and safety study of BXCL501 is expected in the first half of 2019;

Expect data readouts from intravenous (IV) Dex studies supporting BXCL501 development in acute agitation in patients with schizophrenia and senile dementia of the Alzheimer’s type (SDAT) in coming weeks;

Established an industry leading neuro advisory board to support global development of BXCL501 and emerging neuroscience programs.

(BXCL701)-Immuno-Oncology Program-

Received FDA acceptance of IND application for Phase 1b/2 clinical study to evaluate BXCL701 in combination with pembrolizumab (Keytruda) in treatment emergent neuroendocrine prostate cancer (tNEPC); trial initiation is expected in fourth quarter of 2018;

Completed manufacturing of BXCL701 drug product, available for clinical studies;

Selected a leading CRO to support the Company in conducting and managing clinical studies;

Data from the pharmacokinetic, safety and efficacy study of BXCL701 in tNEPC expected to be available throughout 2019;

Entered a clinical immuno-oncology (IO) partnership with Nektar Therapeutics to develop combination of BXCL701, Nektar Therapeutics’ NKTR‑214 and a checkpoint inhibitor as a potential treatment for pancreatic cancer; companies will be sharing the cost of the trial;

Established an industry leading IO clinical advisory board to support global development of BXCL701 and emerging programs.

Emerging Programs-

Continued the use of the artificial intelligence platform to select and prioritize additional pipeline opportunities to augment the current neuroscience and IO portfolio.

Business & Operations-

Strengthened management team with drug development experts including:

Chetan Lathia, Ph.D. as Senior Vice President and Head of Translational Medicine, Clinical Pharmacology and Regulatory Affairs, to support advancement of the pipeline programs.

David Hanley, Ph.D. as Vice President and Head of Global Pharmaceutical Development and Operations, to lead the pharmaceutical development activities and operational efforts.

Vimal Mehta, Ph.D., President and Chief Executive Officer of BTI, commented, "We have made tremendous progress during the past quarter that we believe is truly transformational for BTI. We are well positioned to execute on our clinical programs across our two primary areas of focus."

"In September, we received FDA IND clearance for our first-in-human Phase 1b/2 trial to evaluate BXCL701 in combination with Keytruda as a potential therapy for tNEPC. We anticipate initiating this clinical study prior to year-end. In addition, we expanded our research collaboration with Nektar Therapeutics into a new clinical partnership for further development of the triple combination of BXCL701, Nektar Therapeutics’ NKTR‑214 and a checkpoint inhibitor. Today, we are presenting encouraging preclinical data on the triple combination across multiple tumor models at the 2018 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting. This study demonstrated robust anti-tumor activity resulting in complete tumor regression in certain in vivo models and generation of functional immunological memory, supporting the triple combination as a potential therapy for pancreatic cancer and other tumors."

"Following our productive interactions with the FDA on BXCL501, we plan to initiate our first-in-human pharmacokinetic (bioavailability) and safety trial once our IND is approved. The aim of this trial is to define the optimal dose of BXCL501 and collect sufficient clinical data to proceed to a Phase 3 registration trial in 2019. We have previously reported positive data from our trial of IV Dex, which were essential in determining the ideal dosing strategy. We now expect that data from the IV Dex studies in patients with schizophrenia and SDAT will be available by the end of 2018."

"We are de-risking clinical development of our lead candidates through patient selection optimization, translational research and predictive biomarker discovery utilizing artificial intelligence approaches. Further, we continue to identify additional opportunities for BXCL501 and BXCL701 and plan to pursue their development. We anticipate filing both INDs and clinical trial applications for additional indications across multiple locations, in an effort to establish our global footprint and leverage the significant value of our lead clinical programs."

Dr. Mehta concluded, "We remain firmly committed to our goal of providing patients with transformative therapies while also creating value for our shareholders. We are very excited by

what the future holds for our company and look forward to delivering on the anticipated milestones."

Third Quarter 2018 Financial Results

BTI reported a net loss of $4.9 million for the third quarter of 2018, compared to a net loss of $0.9 million for the same period in 2017.

Research and development expenses were $3.8 million for the third quarter of 2018, as compared to $0.6 million for the same period in 2017. The increase was primarily due to an expansion of research and development activities, including increased personnel costs, professional fees, clinical trials, and manufacturing costs associated with BTI’s two lead drug candidates.

General and administrative expenses were $1.3 million for the third quarter of 2018, as compared to $0.3 million for the same period in 2017. The increase was primarily due to additional payroll and payroll-related expenses, professional fees and costs associated with operating as a public company.

As of September 30, 2018, cash and cash equivalents totaled $47.1 million.

Upcoming investor conferences:

·

Jefferies Global Healthcare Conference, November 14‑15, 2018, London

·

2018 Prescriptions for Success Healthcare Conference, December 12, 2018, New York

·

Investor access event at the J.P. Morgan Healthcare Conference, January 7‑10, 2019, San Francisco

About BXCL501:

BXCL501 is a first in class, sublingual film of dexmedetomidine, a selective alpha 2a receptor agonist for the treatment of acute agitation. BTI believes that BXCL501 directly targets a causal agitation mechanism and has demonstrated anti-agitation effects in preclinical and clinical studies. It has a well-established regulatory and reimbursement path in schizophrenia and bipolar disorder, as demonstrated by a previously-approved drug, Adasuve.

About BXCL701:

BXCL701 is a first in class oral immunotherapy with dual mechanisms of action, with an established safety profile from 700 healthy subjects and cancer patients. Designed to stimulate both the innate and acquired immune systems, BXCL701 works by inhibiting dipeptidyl peptidase (DPP) 8/9 and blocking immune evasion by targeting fibroblast activation protein (FAP). Preclinical combination data evaluating BXCL701, a checkpoint inhibitor and other IO agents has demonstrated encouraging anti-tumor activity in multiple tumor types and formation of functional immunological memory. It is under development for tNEPC and pancreatic cancer.

On November 9, 2018 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading immunotherapy company focused on developing innovative treatments for cancer, autoimmune/inflammatory, and other diseases, reported advancements in the company’s oncology program (Press release, Alpine Immune Sciences, NOV 9, 2018, View Source [SID1234531104]). Following promising preclinical data presented today at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 33rd Annual Meeting in Washington, D.C., the company remains on track to initiate human clinical trials of ALPN-202, a PD-L1/CTLA-4 dual antagonist with PD-L1 dependent CD28 costimulation, in the fourth quarter of 2019. Additionally, Alpine has strengthened its Scientific Advisory Board with the addition of key oncology leaders – Rafi Ahmed, Ph.D., James Welsh, M.D., and John Thompson, M.D.

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ALPN-202 Preclinical Study Results Presented at SITC (Free SITC Whitepaper)’s 33rdAnnual Meeting

Alpine presented the results of a preclinical study of ALPN-202 in a poster session today, strongly supporting the proposed mechanism of action of ALPN-202 via activation of the immune system in a differentiated way from current checkpoint therapies. ALPN-202 is a novel molecule designed to block the inhibitory immune checkpoints PD-L1 and CTLA-4 while providing PD-L1 dependent T cell activation via the CD28 costimulatory pathway. It has previously been demonstrated to have efficacy in an MC38-based colorectal cancer model, superior to the FDA-approved PD-L1 inhibitor durvalumab. Today’s poster correlates these findings with superior intratumoral immune cell infiltration and effector gene signatures, as well as favorable changes in T cell receptor profiles, consistent with ALPN-202’s proposed multi-modal mechanism of action.

"ALPN-202 is differentiated from currently approved checkpoint inhibitors by providing T cell costimulation in addition to dual checkpoint antagonism. We believe that the provision of costimulation, such as via CD28, will be critical to improving response rates during checkpoint inhibition," said Stanford Peng, M.D., Ph.D., Executive Vice President of Research and Development and Chief Medical Officer of Alpine. "In this way, ALPN-202 could result in superior monotherapy efficacy over single or even dual checkpoint antagonists. We anticipate initiating human clinical trials of ALPN-202 for the treatment of advanced malignancies in the fourth quarter of 2019."

The preclinical study evaluated the anti-tumor responses of ALPN-202 compared with durvalumab in mice implanted with human PD-L1 transduced MC38 tumors. Results showed ALPN-202:

Produced dose-dependent anti-tumor responses, including potent single-dose activity
Induced a greater tumor inflammation gene signature than durvalumab
Induced increased T cell infiltration and T cell-related effector gene signatures compared to durvalumab
Promoted both increased T cell receptor clonality and richness, consistent with ALPN-202’s multiple mechanisms of action
NKp30/ICOSL vIgD-Fc program demonstrates tumor-localized costimulation

In a second preclinical study, Alpine used its variant immunoglobin domain (vIgD) platform to engineer novel NKp30/ICOSL vIgD fusion proteins. The resulting therapeutic is designed to agonize two T cell costimulatory receptors ICOS and CD28 only in the presence of B7-H6, a tumor antigen overexpressed in certain cancer types such as some forms of esophageal, kidney, rectal, and stomach cancers.

Results showed the NKp30-ICOSL vIgD-Fc fusion proteins:

Conferred potent T cell costimulation in vitro, with enhanced T cell proliferation and cytokine production only in response to B7-H6-expressing target cells. In contrast, ICOSL and NKp30 vIgDs alone in the absence of B7-H6 were not inflammatory.
Demonstrated efficacy in a B7-H6-positive CT26 mouse colon cancer model, especially when administered in combination with a PD-1 inhibitor. The proteins were not effective on a B7-H6-negative parental CT26 tumors, demonstrating target specificity.
Dr. Peng added, "These results are encouraging because they indicate that NKp30/ICOSL vIgD-Fc fusion proteins in particular may provide a novel therapeutic strategy to provide tumor-specific immunomodulation in a B7-H6-dependent fashion and support the utility of Alpine’s platform in developing novel targeted agents in oncology."

Scientific Advisory Board Appointments

Drs. Rafi Ahmed, James Welsh, and John Thompson have been appointed to the Alpine Immune Sciences Scientific Advisory Board. They join a team of distinguished translational and clinical scientists including Andrew Scharenberg, M.D, Scientific Advisory Board Chair, Manish Butte, M.D, Ph.D, and Paul Tumeh, M.D.

"We welcome Rafi, James, and John to the Alpine Scientific Advisory Board," said Andy Scharenberg, M.D. "The support of these scientific leaders and their belief in Alpine’s vision to bring novel molecules to patients will be important as we work to advance our oncology programs into the clinic next year."

Dr. Rafi Ahmed, Ph.D. is a highly respected researcher who has contributed significant influential work over the past decade in shaping the current understanding of memory T cell differentiation and anti-viral T and B cell immunity. He is the Charles Howard Candler Professor of Microbiology and Immunology at Emory University, where he is also Director of the Emory Vaccine Center, and a Georgie Research Alliance Eminent Scholar in Vaccine Research. He is also a member of the National Academy of Sciences.

"I am looking forward to working with the Alpine team as they have a unique approach of targeting T cells," said Dr. Ahmed. "My lab previously published research showing how CD28/B7 pathway costimulation is required for anti PD-1 antibody efficacy, so I’m particularly excited work with Alpine on their ALPN-202 program."

Dr. James Welsh, M.D. is a Tenured Physician Scientist at The University of Texas MD Anderson Cancer Center, where he serves as the Head of the Immune Radiation program with the goal of using radiation to turn the tumor into an "in-situ" vaccine in order to prime T cells, turning radiation into a systemic therapy. Dr. Welsh and his team recently developed the first mouse model of PD-1 resistance to investigate the mechanisms how cancer cells adapt to evade the immune system.

Dr. John Thompson, M.D. is the Medical Director of the Phase 1 Clinical Trials Program and Co-Director of the Melanoma Clinic at the Seattle Cancer Care Alliance. He also serves as a Professor in the Medical Oncology Division at the University of Washington School of Medicine and is a member of the Clinical Research Division at the Fred Hutchinson Cancer Research Center. Dr. Thompson is a member of several medical societies, including the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), the American Association for Cancer Research (AACR) (Free AACR Whitepaper), the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), and the National Kidney Cancer Association. He has authored or co-authored more than 150 articles, appearing in the Journal of Immunology, Blood Leukemia, Journal of Clinical Oncology, and Clinical Cancer Research, among others.

On November 9, 2018 Unum Therapeutics Inc. (NASDAQ: UMRX), a clinical-stage biopharmaceutical company focused on the development of novel cellular immunotherapies, reported that the Company will present preclinical data on the potential of its proprietary ACTR technology in HER2+ solid tumors and details on the design of its planned Phase 1 clinical trial to test ACTR707 in combination with trastuzumab at the upcoming San Antonio Breast Cancer Symposium taking place December 4-8, 2018 in San Antonio, Texas (Press release, Unum Therapeutics, NOV 9, 2018, View Source [SID1234531190]).

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In preclinical testing, Unum has demonstrated robust activity of its proprietary ACTR T cells in combination with trastuzumab. Importantly, preclinical data demonstrate that, unlike certain CAR-T cells that target HER2, ACTR T cells are highly selective for HER2-overexpressing tumor cells and discriminate against cells from normal tissues that express low levels of HER2. Additionally, the activity of ACTR T cell has been shown to be dose-dependent, demonstrating control of ACTR activity by modulation of trastuzumab concentration. Together these data suggest that ACTR cells in combination with trastuzumab may exhibit an improved clinical therapeutic index.

"We are encouraged by these preclinical data, which further highlight our novel ACTR technology pipeline and demonstrate our innovative approach to overcoming current challenges in the solid tumor setting," said Seth Ettenberg, Chief Scientific Officer of Unum.

"We have an active IND to evaluate ACTR707 in combination with trastuzumab as a potential treatment for HER2+ solid tumor cancers in a Phase I trial called ATTCK-34-01, and we remain on track to initiate this study before the end of 2018," said Michael Vasconcelles, Chief Medical Officer of Unum. "We look forward to continuing our work in the solid tumor setting and reporting initial data in 2019."

ATTCK-34-01 is a multicenter, single-arm, open-label dose escalation study evaluating ACTR T cells in combination with trastuzumab. The primary study objectives are to assess the safety and tolerability of the combination, and to define dose recommendations for further study. Additional objectives include assessment of anti-tumor activity, ACTR T cell persistence and trastuzumab pharmacokinetics.

Details on the presentation are as follows:

Presentation Title: Antibody-Coupled T cell Receptor (ACTR) engineered autologous T cells in combination with trastuzumab for the treatment of HER2-positive malignancies
Session Title: HER2-Targeted Therapy
Date & Time: Thursday, 12/6/18; 5 – 7 PM
Location:Henry G. Gonzalez Convention Center

On November 9, 2018 Bavarian Nordic A/S (OMX: BAVA, OTC: BVNRY) reported its interim financial results in line with guidance for the first nine months of 2018 and business progress for the third quarter of 2018 (Press release, Bavarian Nordic, NOV 9, 2018, View Source [SID1234531089]).

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Highlights

A Biologics License Application for MVA-BN smallpox vaccine (formerly IMVAMUNE) was submitted to the U.S. Food and Drug Administration (FDA). Pending acceptance of the BLA, the Company anticipates approval of the vaccine during 2019 with subsequent filing for a Priority Review Voucher.
IMVANEX smallpox vaccine was supplied to the Public Health England for vaccination of healthcare workers involved in first ever human cases of monkeypox in the U.K.
Following the positive Phase 2 results for our RSV vaccine candidate, MVA-BN RSV, we have initiated discussions with the FDA, which will continue into 2019 with an aim to agree on the design of Phase 3, which we plan to initiate in 2020.
Two studies of our cancer immunotherapy candidate, CV301, in combination with checkpoint inhibitors were initiated. This takes the total number of studies to three, which is in accordance with our strategy to seek rapid proof of concept for the combination of our platform and checkpoint inhibition in three indications. During 2019 we will further advance the potential of our platform by using other routes of administration, which are expected to provide an even broader and more potent anti-tumor response.
A Phase 2 study of BN-Brachyury was initiated in patients with chordoma, a rare cancer in the bones of the skull base and spine with limited treatment options. The vaccine has received orphan drug designation from the FDA for the treatment of chordoma, and the study could potentially provide pivotal results for registration of the vaccine.
Production and deliveries of MVA-BN smallpox vaccine remain on track to fulfil full year guidance.
As planned, Henrik Juuel joined the Company in November as new Chief Financial Officer and member of the executive management.
"The recent BLA submission for our smallpox vaccine highlights the competences and strengths of Bavarian Nordic today, which we proudly apply to advance our technology to develop new vaccines to meet the unmet medical needs that remain in both infectious disease and oncology. We have seen strong progress in our pipeline over the past months with several new studies initiating, seeking proof-of-concept for our immuno-oncology platform across major solid tumor types, but also in rare and underserved cancers, such as chordoma. Following the positive Phase 2 data from our RSV program, we have also recently initiated discussions with the FDA on the design of Phase 3, anticipated to start in 2020. Meanwhile, we continue our successful operations with production of bulk vaccines and construction of our new fill/finish facility going according to plan, securing the foundation for future revenues and success for Bavarian Nordic," said Paul Chaplin, President & Chief Executive Officer of Bavarian Nordic.

Financial results
Financial results for the first nine months were in line with our expectations.

Revenue generated for the nine months ending September 30, 2018 was DKK 319 million/USD 50 million (DKK 1,329 million/USD 206 million in the first nine months of 2017).
The income before interest and tax (EBIT) was a loss of DKK 261 million/USD 41 million (profit of DKK 531 million/USD 82 million in the first nine months of 2017).
As of September 30, 2018, the Group’s cash preparedness was DKK 2,401 million/USD 373 million (DKK 2,604 million/USD 404 million as of December 31, 2017).
Outlook for 2018 maintained
The majority of revenues in 2018 relate to our contract with the U.S. Government for the manufacture of MVA-BN bulk vaccine, all of which have already been produced as of the reporting date. Therefore, we remain on track to fulfill our financial expectations for 2018, with revenues of approximately DKK 500 million/USD 78 million for the full year and a loss before interest and tax (EBIT) of approximately DKK 385 million/USD 60 million. The expected cash preparedness at year-end was upgraded in August from approximately DKK 1,850 million/USD 287 million to approximately DKK 2,100 million/USD 326 million after being granted an unsecured loan facility of EUR 30 million from the European Investment Bank.

Danish kroner (DKK) is the Company’s functional currency. Solely for information purposes, figures above have also been converted into USD using an assumed exchange rate of DKK 6.44 per 1.00 USD, which was the exchange rate as of September 30, 2018.

Anticipated selected pipeline developments

MVA-BN smallpox vaccine

FDA acceptance of the Biologics License Application (BLA) for liquid-frozen MVA-BN (Q4, 2018)
Anticipated FDA approval and award of a Priority Review Voucher (2019)
Initiation of a Phase 3 MVA-BN freeze-dried lot consistency study (H1, 2019)
RSV

Continue discussions with the FDA on the regulatory pathway for approval (H1, 2019)
Initiate Phase 3 study in 2020
Janssen partnership

Initiate Phase 1/2a study of MVA-BN HPV + AdVac (H2, 2018*)
Initiate Phase 1 study of MVA-BN HIV + AdVac (H2, 2018*)
CV301

Report clinical results of NSCLC combination Phase 1/1b (H2, 2018)
Initiate a Phase 1 intra-tumoral administration in patients with solid tumors (H1, 2019)
BN-Brachyury

Report clinical results from Phase 1 study (H2, 2018)
Initiate Phase 1 intravenous administration (H1, 2019)
Report clinical results from Phase 2 in chordoma (H2, 2019)
* Janssen is responsible for the clinical development

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 live and recorded webcast of the presentation can be accessed via View Source To join the Q&A session, use one of the following dial-in numbers: Denmark: +45 35 15 81 21, UK: +44 (0) 330 336 9411, USA: +1 323-794-2551. Participant code is 8332812

On November 9, 2018 Veracyte, Inc. (Nasdaq: VCYT) reported that Bonnie H. Anderson, chairman and chief executive officer, will present at the Canaccord Genuity Medical Technologies & Diagnostics Forum on Thursday, November 15, 2018, at 9:00 a.m. Eastern Time (ET) (Press release, Veracyte, NOV 9, 2018, View Source [SID1234531105]).

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A live audio webcast of the company’s presentation will be available by visiting Veracyte’s website at View Source A replay of the webcast will be available for 90 days following the conclusion of the live presentation broadcast.