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]).

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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.

On April 4, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and DarwinHealth reported they have entered into a research agreement providing Daiichi Sankyo with exclusive access to DarwinHealth’s proprietary novel cancer target database in order to identify potential new targets for cancer drug development (Press release, Daiichi Sankyo, APR 4, 2018, View Source [SID1234525189]).

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DarwinHealth’s proprietary database and technology were created to identify critical mechanisms linked to tumor dependencies and maintenance beyond genetic mutations, and include information on Master Regulators of specific tumor subtypes, as well as direct upstream modulators (both necessary for cancer cell maintenance) across more than 35 tumor and 90 tumor subtypes.

"The purpose of this agreement is to identify novel, high-value cancer targets that can subsequently be prioritized and undergo rigorous experimental validation to drive drug development for a new generation of anti-cancer therapies that would be designed, developed, and owned by Daiichi Sankyo," said Gideon Bosker, MD, Chief Executive Officer, DarwinHealth.

DarwinHealth will receive an upfront payment and has the potential to receive development and commercialization milestone payments should specified events occur relating to DarwinHealth’s novel cancer targets. Daiichi Sankyo will receive exclusive access to DarwinHealth’s novel cancer target database for a predetermined amount of time with an option to extend. Financial terms of the agreement were not disclosed.

We believe that the combination of both molecular and computational techniques used by DarwinHealth coupled with the expertise of our scientists in designing small molecules and antibodies may offer a disruptive approach to accelerating the discovery of precision-medicine cancer compounds," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "This new agreement is a natural next step in expanding our current ongoing translational research collaboration and we look forward to working with DarwinHealth to further science to create meaningful treatments for patients with cancer."

"The novel cancer targets will be selected and prioritized based on their role as either Master Regulators (MRs) or their most specific Master Regulator Upstream Modulators (MRUMs) within a tumor-specific checkpoint module," said Professor Andrea Califano, Co-Founder and Chairman of Scientific and Medical Advisory Board, DarwinHealth. "Therefore, they are expected to represent highly valuable targets for anti-tumor therapy, cancer drug design, and preclinical development."

On April 4, 2018 AstraZeneca and MedImmune, its global biologics research and development arm, reported it will present updates from their early and late stage oncology pipelines at two major congresses this month. In total, 98 abstracts were accepted for the European Lung Cancer Conference (ELCC) in Geneva,11-14 April, and the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in Chicago,14-18 April (Press release, AstraZeneca, APR 4, 2018, View Source [SID1234525172]). The abstracts cover key data updates from the Phase III FLAURA and PACIFIC trials in non-small cell lung cancer (NSCLC), and the Phase III OlympiAD trial in BRCA-mutated metastatic breast cancer. They also highlight promising next-generation research from the company’s extensive pipeline in DNA damage response, Immuno-Oncology and Tumour Drivers & Resistance.

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Dave Fredrickson, Executive Vice President, Head of Oncology Business Unit said: "Building on major regulatory approvals in the first quarter of 2018, AstraZeneca continues to deliver strong results from our innovative science and accelerated development programmes in oncology. At ELCC, we are sharing new data from two pivotal trials in lung cancer that will help inform treatment strategies for patients who, until now, have had very few options. At the AACR (Free AACR Whitepaper) meeting, we will share pioneering early science across multiple tumour types."

ELCC

As part of the ‘Best of ELCC’ sessions, AstraZeneca will present post-progression outcomes from the FLAURA trial of Tagrisso versus the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib or gefitinib in 1st-line EGFR mutation-positive NSCLC (Abstract #128O). In addition, patient-reported outcomes data will also be presented from the FLAURA trial, showing improvements in key symptoms, supporting the potential use of Tagrisso in this setting (Abstract #139PD).

Patient-reported outcomes will be presented from the PACIFIC trial of Imfinzi in unresectable, Stage III NSCLC (Abstract #703), following its approval in the US for this indication.

AACR annual meeting

DNA Damage Response (DDR)

AstraZeneca will present data on its expanded portfolio of potential medicines which exploit DDR dependencies to selectively kill cancer cells across multiple tumour types. The first-in-class PARP inhibitor, Lynparza, will report final overall survival data from the pivotal OlympiAD trial in BRCA-mutated metastatic breast cancer (Abstract #CT038). Data exploring the clinical properties of Lynparza and four other PARP inhibitors will illustrate clinical efficacy and safety profiles (Abstract #LB-273/17).

New data will also be presented on AZD6738, an Ataxia Telangiectasia and Rad3-related (ATR) inhibitor (Abstracts #CT026/19, #LB-263/7 and #337/18) and AZD0156, a first-in-class inhibitor of Ataxia telangiectasia mutated (ATM) (Abstract #4909/5).

Immuno-Oncology (IO)

A series of presentations will share new insights into the science of Imfinzi, including IO-IO combination data from Study 006 (Abstract #CT113) and Study 10 (Abstract #CT113) in 2nd-line NSCLC patient populations.

Beyond Imfinzi, MedImmune will feature progress in its early IO pipeline, including the novel bispecific antibody MEDI5752, designed to target dual checkpoints on immune cells and leverage the synergistic potential of combined mechanisms in immunotherapy (Abstract #2776/9).

Tumour Drivers & Resistance

Data on AZD4573, a CDK9 inhibitor, will demonstrate rapid cell-death induction in haematological tumour models through depletion of MCL1 (Abstract #310/17). And early monotherapy and combination data on the novel ERK inhibitor AZD0364, (Abstract #1647/2) will show its effect on KRAS-mutated tumours when used in combination with MEK inhibitor, selumetinib (Abstract #1856/14).

Crowd-sourcing combinations

AstraZeneca is presenting the results of the DREAM challenge, an open competition combining crowd-sourcing and the application of machine learning to generate new algorithms that predict the best therapeutic combinations for treating different types of cancer (Abstract #3886/5).

AstraZeneca/MedImmune key presentations at ELCC 2018

Lead author

Abstract title

Presentation details

Tagrisso (osimertinib)

Planchard D et al.

Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with untreated EGFRm advanced NSCLC: FLAURA post-progression outcomes

ORAL

Abstract #128O

ESMO-IASLC Best Abstracts

Friday, 13 April

5:30-5:45pm

Room B

Leighl N et al.

Patient-reported outcomes from FLAURA: osimertinib versus standard of care (SoC) epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC)

POSTER DISCUSSION

Abstract #139PD

Thursday, 12 April

8:07am

Room A

Imfinzi

Hui R et al.

Time to deterioration of symptoms with durvalumab in Stage III, locally advanced, unresectable NSCLC: post-hoc analysis of PACIFIC patient-reported outcomes

ORAL

Abstract #703

ESMO-IASLC Best Abstracts

Friday, 13 April

3:00-5:00pm TBD

AstraZeneca/MedImmune key presentations at AACR (Free AACR Whitepaper) 2018 Annual Meeting

Lead author

Abstract title

Presentation details

DNA Damage Response

Robson M et al.

Lynparza

OlympiAD final overall survival: Olaparib versus chemotherapy treatment of physician’s choice (TPC) in patients with HER2-negative metastatic breast cancer (mBC) and a germline BRCA mutation (gBRCAm)

ORAL

Abstract #CT038

Session CTMS01 – New Treatment Approaches for Breast and Ovarian Cancer

Sunday, 15 April

3:50-4:05pm

Room N427 (North, Level 4)

Chen Y et al.

Lynparza + ATM inhibitor

Adaptive oncology phase 1 study of first-in-class inhibitor of ataxia telangiectasia mutated protein kinase (ATM), in combination with olaparib

POSTER

Abstract #4909/5

Session PO.ET05.02 – Pharmacokinetics and Pharmacodynamics

Tuesday, 17 April

1:00-5:00pm

Hall A, Section 41

Krebs M et al.

Lynparza or Imfinzi + ATR inhibitor

Phase I study of AZD6738, an inhibitor of ataxia telangiectasia Rad3-related (ATR), in combination with olaparib or durvalumab in patients (pts) with advanced solid cancers

POSTER

Abstract #CT026/19

Session PO.CT01 – Phase I Clinical Trials 1

Sunday, 15 April

1:00-5:00pm

Hall A, Section 42

Leo E et al.

Lynparza

A head-to-head comparison of the properties of five clinical PARP inhibitors identifies new insights that can explain both the observed clinical efficacy and safety profiles

POSTER

Abstract #LB-273/17

Session LBPO.ET03 – Late-Breaking Research: Experimental and Molecular Therapeutics 3

Tuesday, 17 April

1:00-5:00pm

Hall A, Section 43

Lloyd R et al.

Lynparza + ATR inhibitor

The PARP inhibitor olaparib is synergistic with the ATR inhibitor AZD6738 in ATM deficient cancer cells

POSTER

Abstract #337/18

Session PO.MCB07.03 – Cancer Predisposition and Synthetic Lethality

Sunday, 15 April

1:00-5:00pm

Hall A, Section 15

Young LA et al.

Calquence + ATR inhibitor

Pre-clinical efficacy of AZD6738 in combination with the Bruton’s tyrosine kinase inhibitor, Calquence (acalabrutinib), in models of activated B-cell like diffuse large B-cell lymphoma (DLBCL)

POSTER

Abstract #LB-263/7

Session LBPO.ET03 – Late-Breaking Research: Experimental and Molecular Therapeutics 3

Tuesday, 17 April

1:00-5:00pm

Hall A, Section 43

Immuno-Oncology

Balar A et al.

Durvalumab + tremelimumab in patients with metastatic urothelial cancer

ORAL

Abstract #CT112

Session CTMS02 – Updates in Immuno-oncology Trials

Monday, 16 April

3:35-3:50pm

N Hall C

Chaft J et al.

Phase 1b dose-expansion study of the safety and antitumor activity of durvalumab plus tremelimumab in pretreated advanced NSCLC

ORAL

Abstract #CT113

Session CTMS02 – Updates in Immuno-oncology Trials

Monday, 16 April

3:50-4:05pm

N Hall C

Dovedi SJ et al.

MEDI5752: A novel bispecific antibody that preferentially targets CTLA-4 on PD-1 expressing T-cells

POSTER

Abstract #2776/9

PO.IM02.11 – Therapeutic Antibodies, Including Engineered Antibodies 2

Monday, 16 April

1:00-5:00pm

Hall A, Section 34

O’Donnell P et al.

Updated efficacy and safety profile of durvalumab monotherapy in urothelial carcinoma

POSTER

Abstract #CT031/24

Session PO.CT01 – Phase I Clinical Trials 1

Sunday, 15 April

1:00-5:00pm

Hall A, Section 42

Tumour Drivers & Resistance

Ortiz-Cuaran S et al.

Longitudinal circulating-tumour DNA profiling of EGFR-mutated non-small cell lung cancer patients treated with EGFR-tyrosine kinase inhibitors

ORAL

Abstract #937

Session MS.CL10.01 – Liquid Biopsy 1

Sunday, 15 April

3:20-3:35pm

McCormick Place South (Level 1), Room S105

Cidado J et al.

AZD4573, a novel CDK9 inhibitor, rapidly induces cell death in haematological tumour models through depletion of Mcl1

POSTER

Abstract #310/17

Session PO.MCB02.01 – BCL-2 Family and Mitochondrial Apoptosis

Sunday, 15 April

1:00-5:00pm

Hall A, Section 14

Flemington V et al.

Combination of the novel ERK inhibitor AZD0364 with the MEK inhibitor selumetinib significantly enhances antitumour activity in KRAS mutant tumour models

POSTER

Session PO.ET02.03 – Cell Cycle, Drug Resistance, and Combinations

Abstract #1856/14

Monday, 16 April

8:00am-12:00pm

Hall A, Section 37

Simpson I et al.

Discovery of AZD0364, a potent and selective oral inhibitor of ERK1/2 that is efficacious in both monotherapy and combination therapy in models of NSCLC

POSTER

Abstract (#1647/2)

Session PO.CH01.01 – Target Based Drug Discovery

Monday, 16 April

8:00am-12:00pm

Hall A, Section 30

Innovative Methodologies

Dry JR et al.

A large cancer pharmacogenomics combination screen powering crowd-sourced advancement of computational drug synergy predictions

ORAL

Abstract #3886/5

Session PO.ET05.01 – Pharmacogenetics and Pharmacogenomics

Tuesday, 17 April

8:00am-12:00pm

Hall A, Section 37*

*part of official press programme

On April 4, 2018 DiaMedica Therapeutics Inc. ("DiaMedica") (TSX VENTURE:DMA) (OTCQB:DMCAF), reported that Mr. Rick Pauls, President and CEO, will present at The MicroCap Conference at the Essex House, 160 Central Park South New York on Tuesday April 10th at 12:30pm ET (Press release, DiaMedica, APR 4, 2018, View Source [SID1234525174]).

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The MicroCap Conference is an exclusive event for investors who specialize in small and microcap stocks. It is an opportunity to be introduced to and speak with management at some of the most attractive small companies, learn from various expert panels, and mingle with other microcap investors.

For more information please visit www.microcapconf.com.

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.

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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.