On April 6, 2018 Sanofi reported it will present nine abstracts at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago from April 14-18 (Press release, Sanofi Genzyme, APR 6, 2018, View Source [SID1234525209]). Building on its strong heritage in oncology, the company will share new, early-stage studies highlighting an emerging and dynamic portfolio that encompasses diverse strategies, including immuno-oncology (I-O).

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Sanofi’s abstracts at AACR (Free AACR Whitepaper) will include a late-breaking pre-clinical presentation in partnership with BioNTech highlighting the potential impact of combination treatment with intratumoral cytokine mRNAs, an emerging class of immunotherapy medication. Additionally, results on overcoming resistance to an already-established type of immunotherapy, PD-1 (programmed cell death protein 1) inhibitors, will be presented. Notably, these data will feature Sanofi’s TGF-beta candidate, SAR439459, along with a joint presentation with Evotec on the investigational candidate EVT801, a small molecule inhibitor of VEGFR3 to target myeloid derived suppressor cells (MDSCs) in the tumor microenvironment.

Sanofi is also advancing SAR439859, a SERD (selective estrogen receptor degrader) in estrogen-receptor-positive breast cancer, and will have a number of presentations on this candidate.

"Sanofi is excited to share a broad range of promising early-stage science in oncology at AACR (Free AACR Whitepaper) 2018," said Yong-Jun Liu, M.D., Ph.D., Head of Research, Global R&D at Sanofi. "By strengthening our internal research capabilities, and by collaborating with the key therapeutic leaders in this field, we are now able to demonstrate the emerging strength and depth of our oncology pipeline at Sanofi."

The company is pursuing a breadth of approaches and new technologies to shape its early-stage oncology pipeline, including small molecule therapeutics, next-generation biologics such as antibody drug conjugates, and multi-targeting therapies.

AACR 2018 Data Presentations

Sanofi’s presentations at AACR (Free AACR Whitepaper) 2018 can be accessed via the AACR (Free AACR Whitepaper) website, and are summarized below.

Late breaking presentation

Combinatorial treatment with intratumoral cytokine mRNAs results in high frequency of tumor rejection and development of anti-tumor immunity across a range of preclinical cancer models (Session LBPO.IM01 – Late-Breaking Research: Immunology 1, Section 45, April 16, 2018, 8:00 AM – 12:00 PM)

Oral presentation

SAR439859, an orally bioavailable selective estrogen receptor degrader (SERD) that demonstrates robust antitumor efficacy and limited cross-resistance in ER+ breast cancer (Session MS.EN01.01 – Novel Roles of Steroid Hormone Receptors, Room S504 – McCormick Place South (Level 5), April 15, 2018, 3:05 PM – 3:20 PM)

Sanofi presentation with Evotec

Translation to the clinic of EVT801: A novel immune-oncology agent for addressing innate-driven immunosuppression into the tumor microenvironment and expanding patient population responding to immune checkpoint therapies (PO.IM02.03 – Immune Mechanisms Invoked by Therapies 1, Section 33, April 16, 2018, 1:00 PM – 5:00 PM)

Poster presentations

Pre-clinical development of a novel CD3-CD123 bispecific T-cell engager using Cross-Over-Dual-Variable-Domain (CODV) format for the treatment of acute myeloid leukemia (AML) (Session PO.IM02.10 – Therapeutic Antibodies, Including Engineered Antibodies 1, Section 34, April 16, 2018, 8:00 AM – 12:00 PM)

Sensitivity of liver cancer cell lines to B-catenin knock-down correlates with pathway activation (Session PO.MCB03.03 – Nuclear Oncoproteins and Tumor Suppressor Genes, Section 21, April 16, 2018, 1:00 PM – 5:00 PM)

The anti-TGFβ neutralizing antibody, SAR439459, blocks the immunosuppressive effects of TGFβ and inhibits the growth of syngeneic tumors in combination with anti-PD1 (Session PO.IM02.11 – Therapeutic Antibodies, Including Engineered Antibodies 2, Section 34, April 16, 2018, 1:00 PM – 5:00 PM)

Identification of SAR439859, an orally bioavailable selective estrogen receptor degrader (SERD) that has strong anti-tumor activity in wild-type and mutant ER+ breast cancer models. (Session PO.ET06.10 – Canonical Targets 2, Section 36, April 18, 2018 8:00 AM – 12:00 PM)

Basal-like breast cancer subtype is characterized by deregulated glutamine metabolism and is sensitive to GLS inhibition (Session PO.MCB08.03 – Targets Affecting Metabolism Section 21, April 18, 2018, 8:00 AM – 12:00 PM)

Translational biomarkers for SAR439459, an anti-TGFβ antibody for cancer immunotherapy (PO.CL06.08 – Immunomodulatory Agents and Interventions 3, Section 25, April 18, 2018, 8:00 AM – 12:00 PM)

The agents identified above are under investigation only; their safety and efficacy have not been evaluated by any regulatory authority.

On April 6, 2018 Celltrion reported that it has received a Complete Response Letters (CRLs) from the U.S. Food and Drug Administration (FDA) regarding the Biologics License Application (BLA) for CT-P10 (rituximab), a proposed biosimilar to Rituxan and CT-P6 (trastuzumab), a proposed biosimilar to Herceptin (Press release, Celltrion, APR 6, 2018, View Source [SID1234525568]).

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The FDA Warning Letter issued to Celltrion in January 2018 was directly related to the receipt of the CRL.

Celltrion is making progress addressing the concerns raised by the FDA in a Warning Letter issued in January and is committed to working with the agency to fully resolve all outstanding issues with the highest priority and urgency.

Celltrion is confident that the issues raised by the FDA will be resolved in a timely manner.

We can confirm that the resubmission will be in-place relatively soon. Then, we are expecting approvals in 6 months after resubmission according to regulatory timeline.

(Filing, Annual, Celyad, 2017, APR 6, 2018, View Source [SID1234525205])

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On April 6, 2018 NewLink Genetics Corporation (NASDAQ:NLNK) reported a review of its clinical programs (Press release, NewLink Genetics, APR 6, 2018, View Source [SID1234525805]).

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This morning’s announcement by Incyte and Merck on the ECHO-301 trial for patients with advanced melanoma is a disappointing result for the IDO field. Indoximod, NewLink Genetics’ IDO pathway inhibitor, has a differentiated mechanism of action (MOA) which may demonstrate clinical benefit for patients where direct enzymatic inhibitors have not. In light of Incyte’s announcement, however, NewLink is undertaking a review of its clinical programs and will provide an update when it is completed.

NewLink Genetics has generated data for indoximod across several indications, and in combination with different modalities, suggesting the potential for indoximod to improve the outcomes for patients with cancer. The Company will present additional data at AACR (Free AACR Whitepaper) next week, including a poster presentation further supporting indoximod’s differentiated MOA and a plenary session presenting encouraging early clinical data of indoximod plus radiation for pediatric patients with diffuse intrinsic pontine glioma (DIPG), a rare and lethal form of brain cancer.

About Indoximod

Indoximod is an investigational, orally available small molecule targeting the IDO pathway. The IDO pathway is a key immuno-oncology target involved in regulating the tumor microenvironment and immune escape. Indoximod is being evaluated in combination with treatment regimens including anti-PD-1/PD-L1 agents, cancer vaccines, radiation, and chemotherapy across multiple indications such as melanoma, pancreatic cancer and other malignancies.

On April 5, 2018 SignalRx Pharmaceuticals Inc., a clinical-stage company developing novel small-molecules therapeutics via in-silico design to simultaneously inhibit multiple key orthogonal and synergistic oncotargets for the treatment of cancer, reported the presentation of its novel triple CDK4-6/PI3K/BRD4 inhibitor program and first-in-class triple inhibitor SRX3177 (Press release, SignalRx, APR 5, 2018, http://www.ireachcontent.com/news-releases/signalrx-to-present-on-its-first-in-class-triple-cdk4-6pi3kbrd4-inhibitor-srx3177-for-treating-cancer-at-the-13th-annual-drug-discovery-chemistry-2018-meeting-678885923.html [SID1234527318]). The presentation by Donald L. Durden, MD, PhD, senior scientific advisor for SignalRx, will be at 2:20 pm on Thursday April 5th, 2018, in the Small Molecules for Cancer Immunotherapy session at the Drug Discovery Chemistry 2018 meeting in San Diego, CA. Data related to combinatorial small molecules which strike multiple immune-oncology cancer targets and activate the innate and adaptive anti-tumor immune response will be presented. The Small Molecules for Cancer Immunotherapy session will also be chaired by Dr. Durden.

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Using SignalRx’s proprietary CRIMP technology platform, the company designed SRX3177 to inhibit three key cancer-driving oncotargets with one drug: CDK4/6, PI3K and BRD4. SRX3177 results in synergistic synthetic lethality in cancer cells (e.g., breast cancer, mantle cell lymphoma) because this novel anticancer agent addresses the following critical cancer-driving facts:

PI3K inhibition abrogates resistance to CDK4/6 inhibition.
BRD4 inhibition decreases transcription of cyclin D1 and MYC.
MYC inhibition decreases levels of immuno-oncology targets CD47 and PD-L1.
CDK4/6 inhibition activates the AKT pathway.
"SignalRx designs all its novel chemotypes and drugs in silico. Because not a single chemotype comes from screening commercially available compounds, SignalRx has built and continues to build a strong and proprietary pipeline" said Dr. Donald L. Durden, founder and senior scientific advisor of SignalRx Pharmaceuticals and Professor and Associate Director of Pediatric Oncology at the Moores UCSD Cancer Center.

The profile of in silico designed small-molecule triple inhibitor SRX3177 includes:

Picomolar CDK4 inhibition potency.
Double-digit nM PI3K and BRD4 inhibitory potency.
BRD4-BD1 selective (5 X) vs BRD4-BD2.
5 Fold more potent than Palbociclib as CDK4 inhibitor.
19-80 Fold more potent than Palbociclib in 3 in vitro cancer cell assays.
40 Fold less toxic in normal epithelial cells vs corresponding combination of three separate inhibitors (Palbociclib + BKM120 + JQ1).
Induction of cell cycle arrest and increased apoptosis.
Lethal in 85% of the cancer cell lines tested in NCI 60 cancer-cell panel.
"All our chemotypes are small molecules (no linking moieties used). Because we rationally design all our anticancer agents from the beginning, we know how to tune in and out target affinity in our compounds. We are in an excellent position to also explore CDK4/6-BRD4 and CDK4/6-PI3K single small-molecule inhibitors for cancer and other applications" said Dr. Joseph Garlich, SignalRx’s Chief Scientific Officer.

SignalRx is also seeking partnering opportunities to accelerate the development of its programs and advance novel anticancer therapeutics into first-in-man clinical trials based on the promising profile and mode of action of its inhibitors. Since these are single molecules with a single PK/PD and toxicity profile, there is a great opportunity to streamline their development alone and in combination therapies.