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Nordic Nanovector provides update on the PARADIGME clinical trial

On April 4, 2018 Nordic Nanovector ASA (OSE: NANO) reported an update on its clinical development programme, including updated guidance on expected milestones for the pivotal PARADIGME trial, and its financial outlook (Press release, Nordic Nanovector, APR 4, 2018, View Source [SID1234553508]). A presentation by the company’s management team will take place tomorrow in Oslo at 10 am CEST, see details below.

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• A re-assessment of expected recruitment rates has led the company to revise its timelines for the pivotal PARADIGME Phase 2b trial with Betalutin in third line (3L) follicular lymphoma (FL) patients. Results from PARADIGME are targeted for 1H 2020 (previously 2H 2019) and first regulatory filing in 2020. The first patient is expected to be dosed in 1H 2018.

• The company will focus its resources towards PARADIGME and other Betalutin clinical programmes, which has led to the decision to postpone the start of the first-in-human clinical trial with Humalutin for the foreseeable future; this study was being prepared to start in 2H 2018.

• Guidance is unchanged for previously reported milestones for ARCHER-1 (Betalutin plus rituximab in second line FL; first patient dosed) and LYMRIT 37-05 (Betalutin in R/R diffuse large B cell lymphoma, DLBCL; preliminary data read-out), both anticipated in 2H 2018.

• Financial resources are expected to be sufficient to reach data read-out from PARADIGME

Lisa Rojkjaer MD, Nordic Nanovector CMO, said: "While we are encouraged with the progress being made to the start-up of the pivotal PARADIGME study, a re-analysis of the patient enrolment rate and the fact that it has taken longer than expected to enrol the first patient have led us to adjust the timelines we previously communicated. We now expect to deliver data from PARADIGME in the first half of 2020.

"The PARADIGME study reflects our conviction in the significant potential of Betalutin based on the promising clinical data generated to-date. We therefore remain committed to completing this robust study, which is designed to select the best dosing regimen to support Betalutin as an important new treatment option for 3L FL patients."

PARADIGME – clear focus for company

PARADIGME is a global randomised Phase 2b study comparing two Betalutin dosing regimens in 3L R/R FL patients, which have shown a promising clinical profile in the LYMRIT 37-01 Phase 1/2a trial. The pivotal PARADIGME study was initiated at the end of 2017 in Europe and the first patient is expected to be dosed during the first half of 2018. The trial is aiming to enrol 130 patients in 20 countries.

To date, PARADIGME is open for enrolment at 13 sites and in six countries.

In Norway, PARADIGME is pending approval and the company is working closely with the Norwegian regulators to address its questions.

In the USA, the Food & Drug Administration (FDA) has completed its review of the PARADIGME study and Nordic Nanovector expects US sites to be open for enrolment during mid-2018.

Humalutin – first human trials postponed

Nordic Nanovector was preparing a Phase 1 study of Humalutin, a novel 177Lu-conjugated chimeric anti-CD37 antibody, in NHL patients. The company previously guided that it expected to start this study in the second half of 2018. As a consequence of the revised timelines for PARADIGME and the need to conserve cash until data read-out, Nordic Nanovector has decided to put the Humalutin study on hold for the foreseeable future.

ARCHER-1 and LYMRIT 37-05 – on track

ARCHER-1 is a planned clinical study designed to evaluate the safety and efficacy of combining Betalutin with rituximab in second line (2L) FL patients. The company expects the first patient to be dosed in the second half of 2018 as previously guided.

LYMRIT 37-05 is an on-going Phase 1 study evaluating Betalutin in patients with R/R DLBCL. As previously guided, the company expects preliminary data read-out from this study in the second half of 2018.

Presentation and webcast

A presentation by Nordic Nanovector’s management team will take place tomorrow at 10 am CEST at:

Thon Hotel Vika Atrium, Munkedamsveien 45, 0250 Oslo

Meeting Room: Aker

The presentation will be recorded as a webcast and will be available, with the presentation, at www.nordicnanovector.com in the section: Investors & Media

Arvinas Completes $55 Million Series C Financing to Advance Protein Degradation Platform

On April 4, 2018 Arvinas LLC, a private biotechnology company creating a new class of drugs based on protein degradation, reported the closing of a $55 million Series C financing (Press release, Arvinas, APR 4, 2018, View Source [SID1234529237]). The financing was led by new investor Nextech Invest, with participation from additional new investors Deerfield Management, Hillhouse Capital, and Sirona Capital. All existing investors also participated in this financing round, including Canaan Partners, 5AM Ventures, RA Capital Management, OrbiMed, and New Leaf Venture Partners.

Proceeds from the financing will support the advancement of the Company’s two lead programs toward clinical investigation. The two programs, which target the androgen receptor for castration resistant prostate cancer and the estrogen receptor for ER+ positive breast cancer, both nominated orally available clinical candidates in the fourth quarter of 2017. These proceeds will also advance the Company’s early stage oncology pipeline, CNS pipeline, and efforts on undruggable targets.

"This past year has been exciting for us with two clinical candidate nominations, the expansion of our collaboration with Genentech and the announcement of a new collaboration with Pfizer," said John Houston, Ph.D., President and Chief Executive Officer of Arvinas. "With this additional financial support from existing and new investors who believe in our innovative protein degradation platform, we will continue executing on our strategy of progressing our lead programs to the clinic, expanding the use of the platform outside of oncology, and tackling undruggable targets."

In connection with the financing, Jakob Loven, Ph.D., partner with Nextech Invest, will join the Arvinas board of directors.

"The Arvinas PROTAC platform is an elegant, novel therapeutic modality that circumvents delivery challenges associated with existing therapeutic approaches to eliminate protein function, and Arvinas has proven to be the clear leader in developing a new era of targeted medicines using its protein degradation technology," said Dr. Loven.

The Company’s PROTAC Platform offers potential improvements over traditional small molecule inhibitors by using the cell’s natural and selective ubiquitin proteasome system to degrade disease-causing proteins. By removing target proteins directly rather than simply inhibiting them, PROTACs can provide multiple advantages over small molecule inhibitors which can require high systemic exposure to achieve sufficient inhibition, often resulting in toxic side effects and eventual drug resistance. With multiple protein targets, Arvinas’ PROTAC platform has demonstrated that a transient binding event at a range of binding sites and affinities can translate into very potent degradation of the target protein.

Molecular Partners to present MP0310 pre-clinical data and MP0250 clinical abstracts at the AACR Annual Meeting 2018

On April 4, 2018 Molecular Partners AG (ticker: MOLN), a clinical-stage biopharmaceutical company developing a new class of drugs known as DARPin therapies*, reported that new pre-clinical data from two of its pipeline candidates, MP0310 and its lead proprietary oncology drug MP0250, as well as the DARPin toolbox will be presented at the Annual Meeting 2018 of the American Association of Cancer Research (AACR) (Free AACR Whitepaper) in Chicago (Press release, Molecular Partners, APR 4, 2018, View Source [SID1234525191]).

MP0310 targets simultaneously 4-1BB and FAP and is the first of a series of tumor-restricted agonists that only activate immune cells in the tumor and not in the rest of the body thereby allowing full activation and potentially opening the therapeutic window for combinations.

MP0250 is a phase 2 multi-DARPin candidate targeting simultaneously VEGF and HGF, two prominent escape pathways, and has the potential to reverse resistance that has built to standard of care cancer therapies.

The four abstracts to be presented include the most recent pre-clinical data of MP0310 as well as the rationale of MP0250 in EGFR mutated NSCLC (Non-small Cell Lung Cancer).

"We are very pleased with the progress of our portfolio showcasing the innovation power of the DARPin technology in the multi-specific biologics space," commented Michael T. Stumpp, Chief Scientific Officer. "With MP0250 and MP0310, we are moving forward with two candidates that have the potential to add significant patient benefit and support existing therapies."

The data will be presented in the following sessions under the following titles:

MP0310:
Tuesday, 17 April 2018, 8.00 am: PO.IM02.07 – Immunomodulatory Agents and Interventions 1: 3752 / 2 – Preclinical pharmacology of MP0310: A 4-1BB/FAP bispecific DARPin drug candidate promoting tumor-restricted T-cell co-stimulation (Link et al.)
Tuesday, 17 April 2018, 8.00 am: PO.TB07.01 – Cancer Imaging: Immunology and Systems Analysis in Vivo: 3029 / 2 – FAP-mediated tumor accumulation of a T-cell agonistic FAP/4-1BB DARPin drug candidate analyzed by SPECT/CT and quantitative biodistribution
(Reichen et al.)
Portfolio:
Tuesday, 17 April 2018, 1.00 pm: PO.CL06.05 – Immune Checkpoints 4: 4552 / 7 – Tumor-restricted immune modulation by multispecific molecules from the DARPin toolbox (Fiedler et al.)
MP0250:
Tuesday, 17 April 2018, 1.00 pm: PO.CT05 – Phase I/II, II, and III Trials in Progress: CT149 / 1 – MP0250, a VEGF- and HGF-blocking multi-DARPin drug candidate, in combination with tyrosine-kinase-inhibitors targeting EGFR-mutated NSCLC: Preclinical rationale and phase Ib/II study outline (Kiemle-Kallee et al.)
Full details on the Molecular Partners’ sessions at AACR (Free AACR Whitepaper) 2018 as well as all presentations can be found here. Following their presentation at the AACR (Free AACR Whitepaper), the posters will also be available one the Molecular Partners website.

About the DARPin Difference
DARPin therapeutics are a new class of protein therapeutics opening an extra dimension of multi-specificity and multi-functionality. DARPin candidates are potent, specific, safe and very versatile. They can engage in more than 5 targets at once, offering potential benefits over those offered by conventional monoclonal antibodies or other currently available protein therapeutics. The DARPin technology is a fast and cost-effective drug discovery engine, producing drug candidates with ideal properties for development and very high production yields.

With their good safety profile, low immunogenicity and long half-life in the bloodstream and the eye, DARPin therapies have the potential to advance modern medicine and significantly improve the treatment of serious diseases, including cancer and sight-threatening disorders. Molecular Partners is partnering with Allergan to advance clinical programs in ophthalmology, and is advancing a proprietary pipeline of DARPin drug candidates in oncology. The most advanced global product candidate is abicipar, a molecule currently in Phase 3, in partnership with Allergan.

Several DARPin molecules for various ophthalmic indications are also in development. The most advanced systemic DARPin molecule, MP0250, is in Phase 1 clinical development for the treatment of solid tumors and in Phase 2 development for hematological tumors. In addition, Molecular Partners intends to further evaluate MP0250 for solid tumors in a phase 1b/2 trial for EGFR-mutated NSCLC. MP0274, the second-most advanced DARPin drug candidate in oncology, has broad anti-HER activity; it inhibits HER1, HER2 and HER3-mediated downstream signaling via Her2, leading to induction of apoptosis. MP0274 has moved into Phase 1. Molecular Partners is also advancing a growing preclinical pipeline that features several immuno-oncological development programs. DARPin is a registered trademark owned by Molecular Partners AG.

Compugen, AstraZeneca unit in cancer drug development deal

On April 4, 2018 Compugen Ltd. (NASDAQ: CGEN), a leader in predictive discovery and development of first-in-class therapeutics for cancer immunotherapy, reported it entered into an exclusive license agreement with MedImmune, the global biologics research and development arm of AstraZeneca, to enable the development of bi-specific and multi-specific immuno-oncology antibody products (Press release, Compugen, APR 4, 2018, View Source [SID1234525602]).

Under the terms of the agreement, Compugen will provide an exclusive license to MedImmune for the development of bi-specific and multi-specific antibody products derived from a Compugen pipeline program. MedImmune has the right to create multiple products under this license and will be solely responsible for all research, development and commercial activities under the agreement. Compugen will receive a $10 million upfront payment and is eligible to receive up to $200 million in development, regulatory and commercial milestones for the first product as well as tiered royalties on future product sales. If additional products are developed, additional milestones and royalties would be due to Compugen. Compugen will retain all other rights to its entire pipeline of programs as monotherapies and in combination with other products.

"We are excited to announce our agreement with MedImmune, a global leader in the development of antibody-based oncology therapeutics," said Anat Cohen-Dayag, PhD, President and CEO of Compugen. "This licensing deal allows us to monetize specific scientific advances in our programs, while we continue to advance our lead programs into clinical trials." Dr. Cohen-Dayag added, "We are committed to our strategy of selectively collaborating with biopharmaceutical companies for the development of first-in-class products against our diverse, computationally-derived portfolio of targets."

"This agreement with Compugen will support our abilities to generate novel immunotherapy targets which, coupled with MedImmune’s expertise in antibody engineering, can advance our goal of delivering treatments to meaningfully improve the lives of cancer patients," said Ronald Herbst, Vice President, Oncology Research & Development, MedImmune.

Conference Call and Webcast Information

Compugen management will host a conference call today, April 2, 2018, at 8:30 a.m. ET to discuss the license agreement. To access the live conference call by telephone, please dial 1-800-994-4498 from the U.S. or +972-3-918-0608 internationally. The conference call will also be available via live webcast through Compugen’s website, located at the following link. Following the live audio webcast, a replay will be available on the Company’s website.

About Bi-Specific and Multi-Specific Products

Antibodies are naturally occurring components of the immune system that bind specifically to a target protein via two identical arms. Through genetic engineering, antibodies can be modified to bind to different proteins through the two separate arms by exchanging one arm with that of another antibody with a different target specificity (bi-specific antibodies). Alternatively, additional features can be engineered into an antibody to allow binding to three or more target proteins simultaneously (multi-specific antibodies). These engineered forms of antibodies are increasingly being developed as therapeutics, as they enable multiple mechanisms of action for treating disease within a single molecule.

Eleven Biotherapeutics Reports Fourth Quarter and Full-Year 2017 Operating Results and Vicinium Development Progress

On April 4, 2018 Eleven Biotherapeutics, Inc. (NASDAQ: EBIO), a late-stage clinical company developing next-generation antibody-drug conjugate (ADC) therapies for the treatment of cancer, reported key pipeline progress and operating results for the quarter and year ended December 31, 2017 (Press release, Eleven Biotherapeutics, APR 4, 2018, View Source [SID1234525196]).

"2017 was a year of significant developments for our company, and as we look ahead, I am highly encouraged by what we have already achieved in 2018. Vicinium, our lead product candidate, holds significant potential in treating a range of cancers, and is well underway in a registration trial for people with non-muscle invasive bladder cancer," said Stephen Hurly, president and chief executive officer of Eleven Biotherapeutics. "We recently completed enrollment in our Phase 3 VISTA trial, and we are pleased that initial data from the first patients in the VISTA trial were selected for an oral presentation at the American Urological Association Annual Meeting. 2018 is set to be a transformative year, and with the completion of our recent equity financing, we are capitalized to continue advancing Vicinium. We look forward to assessing its efficacy and safety in NMIBC, and exploring opportunities to expand its utility in other indications and in combination regimens."
Recent Pipeline and Corporate Highlights

On March 23, 2018, Eleven Biotherapeutics closed a $10.0 million equity financing priced at-the-market. This financing, coupled with the proceeds from the company’s $8.0 million public offering completed in November 2017, extends the company’s cash runway into the first quarter of 2019 based on its current operating plan.

In March 2018, Eleven Biotherapeutics announced that enrollment was completed in the company’s Phase 3 VISTA trial evaluating its lead product candidate, Vicinium, for the treatment of patients with non-muscle invasive bladder cancer (NMIBC) who have been previously treated with bacillus Calmette-Guérin (BCG).

In December 2017, a trial at the US National Cancer Institute (NCI) of Vicinium in combination with AstraZeneca’s immune checkpoint inhibitor, Imfinzi (durvalumab), for the treatment of NMIBC opened.

In September 2017, Eleven Biotherapeutics completed the manufacturing of all Vicinium necessary for its ongoing trials.
Upcoming Data Presentations

Present Preclinical Data at AACR (Free AACR Whitepaper): Eleven Biotherapeutics will present preclinical data from its deBouganin program at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting during two poster sessions. The company’s systemically administered product candidates are designed using its proprietary de-immunized variant of the plant-derived cytotoxin bouganin, deBouganin. Details of the presentations are as following:

Poster Title: VB6-845d Tumor Cell Killing Elicits Biologic Features of Immunogenic Cell Death

Date and Time: April 16, 2018 from 1:00 to 5:00 p.m. CT

Poster Title: Engineering and Characterization of Anti-PSMA Humabody-DeBouganin Fusion Proteins

Date and Time: April 18, 2018 from 8:00 a.m. to 12:00 p.m. CT

Present Data from Phase 3 VISTA Trial at AUA Annual Meeting: Eleven Biotherapeutics will present the first, topline data from its Phase 3 VISTA trial of Vicinium in patients with NMIBC who have been previously treated with BCG during a plenary session at this year’s American Urological Association Annual Meeting being held in San Francisco. The data being presented are three-month data from an initial 75 patients in the trial. Details of the presentation are as follows:

Presentation Title: Phase 3 Study of Vicinium in BCG-Unresponsive Non-Muscle Invasive Bladder Cancer: Initial Results

Date and Time: Monday, May 21, 2018 at 11:00 a.m. PT
Fourth Quarter and Full-Year 2017 Financial Results

Cash Position: Cash and cash equivalents were $14.7 million as of December 31, 2017, compared to $25.3 million as of December 31, 2016, a decrease of $10.6 million, which was primarily driven by $17.6 million in cash used by operating activities plus, $0.1 million in capital expenditures, partially offset by $7.1 million in cash provided through the November 2017 underwritten public offering.

Revenue: No revenue was recognized during the three months ended December 31, 2017, compared to $0.8 million for the same three-month period in 2016. Revenue was $0.4 million for the twelve months ended December 31, 2017, compared to $30.0 million for the same period in 2016. The decrease was primarily due to a decrease in license revenue as we recognized the upfront license fee and development milestone payment under the license agreement with Roche, relating to the execution of the license agreement and the successful submission of the IND application for EBI-031 during 2016, as well as a decrease in collaboration revenue from a terminated collaboration.

R&D Expenses: Research and development expenses were $3.1 million for the three months ended December 31, 2017, compared to $2.8 million for the same period in 2016. For the twelve months ended December 31, 2017 research and development expenses were $12.5 million compared to $13.5 million for the 2016 fiscal year. The decrease of $1.0 million was primarily due to a decrease in EBI-031 related development expenses of $3.0 million due to the license agreement with Roche in which Roche is responsible for all on-going development expenses, as well as a decrease of $1.7 million of isunakinra-related development expenses, which development activities are no longer ongoing. These decreases were partially offset by increases in Vicinium-related development

elevenlogoa06.jpg

expenses of $5.4 million, since the company’s acquisition of Viventia Bio Inc. (Viventia) in September 2016.

G&A Expenses: General and administrative expenses were $2.0 million for the three months ended December 31, 2017, compared to $2.8 million for the same period in 2016. For the twelve months ended December 31, 2017 general and administrative expenses were $8.1 million compared to $14.7 million for fiscal 2016. The decrease of $6.7 million was primarily due to a reduction of professional fees as well as salaries and related costs for personnel, including stock-based compensation. For the year ended December 31, 2016, the company had higher professional fees related to the license agreement with Roche, the company’s 2016 review of strategic alternatives and the acquisition of Viventia. In addition, for the year ended December 31, 2016, the company recorded higher severance costs related to the acquisition of Viventia.

Net Income (Loss): Net loss was $6.6 million, or $0.22 per share, for the three months ended December 31, 2017, compared to net loss of $3.5 million, or $0.15 per share, for the same period in 2016. Net loss was $29.0 million, or $1.11 per share, for the twelve months ended December 31, 2017, compared to net income of $1.9 million, or $0.09 per share, for the same period in 2016. Fiscal 2016 was benefited by approximately $30.0 million in revenue under the company’s license agreement with Roche while no comparable revenue was recognized during fiscal 2017.

Financial Guidance: Following Eleven Biotherapeutics’ recent $10.0 million equity financing in March 2018, the company expects to have capital to fund its current operating plans into the first quarter of 2019; however, we have based this estimate on assumptions that may prove to be wrong, and our capital resources may be utilized faster than we currently expect.
About Vicinium
Vicinium, Eleven Biotherapeutics’ lead product candidate, is a next-generation antibody-drug conjugate (ADC) developed using the company’s proprietary Targeted Protein Therapeutics platform. Vicinium is comprised of a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas Exotoxin A (ETA). Vicinium is constructed with a stable, genetically engineered peptide linker to ensure the payload remains attached until it is internalized by the cancer cell, which is believed to decrease the risk of toxicity to healthy tissues, thereby improving its safety. In prior clinical studies conducted by Eleven Biotherapeutics, EpCAM has been shown to be overexpressed in non-muscle invasive bladder cancer (NMIBC) cells with minimal to no EpCAM expression observed on normal bladder cells. Eleven Biotherapeutics is currently conducting the Phase 3 VISTA trial, designed to support the registration of Vicinium for the treatment of NMIBC in patients who have previously received two courses of bacillus Calmette-Guérin (BCG) and whose disease is now BCG-unresponsive. Topline, three-month data from the trial are expected in mid-2018. Additionally, Eleven Biotherapeutics believes that Vicinium’s cancer cell-killing properties promote an anti-tumor immune response that may potentially combine well with immuno-oncology drugs, such as checkpoint inhibitors. The activity of Vicinium in BCG-unresponsive NMIBC is also being explored at the US National Cancer Institute in combination with AstraZeneca’s immune checkpoint inhibitor durvalumab.